CYP2D6 rs4924576: Understanding This Pharmacogenomic Marker
The genetic variant rs4924576 is an intronic single nucleotide polymorphism located within the complex CYP2D6 gene cluster on chromosome 22. In pharmacogenomics, this marker frequently acts as an informative tagging variant for broader haplotype structures that govern hepatic drug metabolism. Because it resides in a non-coding region, its direct functional impact is limited, and it serves primarily as an indicator of surrounding variation within the cytochrome P450 pathway.
What each genotype means
Typical metabolic marker
This genotype represents the major allele configuration for this specific intronic marker. While this marker is associated with the CYP2D6 gene cluster, it is not a direct functional variant and does not independently determine your metabolic status. Please consult with your clinician or pharmacist regarding any medications metabolized by the CYP2D6 enzyme, as clinical phenotype is determined by complex star-allele combinations.
This is a common genotype observed in a significant portion of the global population, with frequencies varying by ancestry.
Typical metabolic marker
This genotype indicates you carry one copy of the minor allele at this intronic position. This marker is used to tag variation within the CYP2D6 gene region, but it does not directly alter enzyme activity on its own. Because CYP2D6 function is highly complex and influenced by many different genetic factors, you should discuss your medication response and dosing with a healthcare provider.
This heterozygous genotype is frequently found across diverse populations, often appearing in 30% to 50% of individuals depending on ethnic background.
Typical metabolic marker
This genotype represents the homozygous minor allele state for this intronic marker. This variant serves as a tag for the CYP2D6 gene cluster but is not considered a primary functional driver of enzyme activity. As CYP2D6-related drug metabolism is complex and depends on multiple genetic factors, please discuss any concerns about medication efficacy or safety with your doctor or pharmacist.
This genotype is common in many populations, though its prevalence varies significantly across different ancestral groups.
Genomic Location and Variant Classification
The single nucleotide polymorphism rs4924576 is situated on chromosome 22q13.2 inside an intronic region of the cytochrome P450 2D6 (CYP2D6) gene cluster according to databases such as [dbSNP rs4924576](https://www.ncbi.nlm.nih.gov/snp/rs4924576). Because it resides outside the protein-coding exons, it does not directly alter the amino acid sequence of the resulting enzyme. Instead, genetic research frequently utilizes rs4924576 as a tagging single nucleotide polymorphism, meaning it is inherited in linkage disequilibrium alongside other critical variants within the locus. The CYP2D6 genomic region is exceptionally complex, containing the functional CYP2D6 gene adjacent to highly similar pseudogenes like CYP2D7, which frequently exchange sequence material through gene conversion and structural rearrangement as detailed in comprehensive reviews ([Taylor et al., 2020](https://pmc.ncbi.nlm.nih.gov/articles/PMC7692531/)). Consequently, single intronic markers such as rs4924576 provide useful structural context across the region but do not themselves represent a causal metabolic defect.
The Biological Role of CYP2D6 in Drug Metabolism
The CYP2D6 gene encodes an essential hepatic microsomal enzyme that belongs to the cytochrome P450 superfamily. Despite representing only a modest portion of total liver enzyme content, CYP2D6 is responsible for metabolizing approximately 20 percent of commonly prescribed medications across cardiovascular medicine, psychiatry, oncology, and pain management ([Taylor et al., 2020](https://pmc.ncbi.nlm.nih.gov/articles/PMC7692531/)). This pathway processes vital drug classes such as beta-blockers, selective serotonin reuptake inhibitors, tricyclic antidepressants, and opioid analgesics like tramadol and codeine ([Medical Genetics Summaries](https://www.ncbi.nlm.nih.gov/books/NBK315950/)). Inherited genetic changes across the CYP2D6 locus can drastically alter how quickly the body clears these drugs or converts inactive prodrugs into their therapeutic active metabolites. The clinical consequences range from inadequate drug response due to rapid clearance to toxic drug accumulation or excessive opioid metabolite exposure, highlighting the enzyme's outsized importance in individualized pharmacology.
Strength of Evidence and Tagging Limitations
In pharmacogenomic research, evidence connecting isolated intronic single nucleotide polymorphisms directly to clinical drug responses is classified as limited. While genome-wide association studies sometimes flag rs4924576 due to statistical linkage with regional drug clearance variations, clinical practice guidelines developed by bodies such as the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group do not rely on rs4924576 alone ([Medical Genetics Summaries](https://www.ncbi.nlm.nih.gov/books/NBK574601/)). Instead, clinical translation utilizes 'star allele' haplotypes (such as CYP2D6*4, *10, or *17) defined by combinations of specific coding variants, small indels, and structural copy number variations ([Jiang et al., 2024](https://www.medrxiv.org/content/10.1101/2024.07.23.24310892v1.full-text)). An intronic marker like rs4924576 may travel alongside a functional haplotype in one specific ancestry while uncoupling from it in another, meaning it lacks universal diagnostic power on its own.
Population Frequency and Ancestral Diversity
The single nucleotide polymorphism rs4924576 is a common marker across diverse global populations, displaying major allele frequencies that typically vary between 30% and 50% depending on geographic ancestry. Because the CYP2D6 locus exhibits extraordinary global genetic diversity, haplotype architectures differ fundamentally between continents ([Medical Genetics Summaries](https://www.ncbi.nlm.nih.gov/books/NBK574601/)). For instance, structural duplications and decreased-function alleles like CYP2D6*10 predominate in East Asian cohorts, whereas no-function alleles like CYP2D6*4 are far more frequent in European populations ([Jiang et al., 2024](https://www.medrxiv.org/content/10.1101/2024.07.23.24310892v1.full-text)). Because rs4924576 has evolved within these divergent ancestral backgrounds, the underlying functional alleles with which it correlates can vary substantially, reinforcing why population context is essential when interpreting non-coding pharmacogenomic markers.
Clinical Translation and Reader Guidance
Discovering an rs4924576 genotype on a consumer genetic test or research panel provides interesting biological insight, but it cannot be used in isolation to guide healthcare choices. An individual variant in an intron does not confirm whether a person is an ultrarapid, normal, intermediate, or poor metabolizer of prescription drugs. Formal clinical pharmacogenetic testing requires comprehensive laboratory assays capable of detecting copy number variations, gene deletions (such as CYP2D6*5), and multi-variant haplotypes ([Taylor et al., 2020](https://pmc.ncbi.nlm.nih.gov/articles/PMC7692531/)). Readers should never adjust medication doses, discontinue therapy, or initiate new drugs based on raw genetic data. Anyone with questions regarding how their genetics might influence medication safety or effectiveness should seek a consultation with a prescribing physician, a licensed genetic counselor, or a clinical pharmacologist.
How common is this variant?
This polymorphism is common across human populations, with major allele frequencies generally ranging between 30% and 50% across diverse global ancestries.
Frequently asked questions
Can rs4924576 tell me if I am a poor or rapid metabolizer?
No, rs4924576 alone cannot determine your overall CYP2D6 metabolizer status. Metabolizer categories depend on comprehensive star-allele definitions that evaluate multiple coding variants, gene duplications, and structural rearrangements across the entire CYP2D6 gene.
Should I alter my medication dose if I carry a minor allele at rs4924576?
You should never modify your prescription dosage or stop taking any medication based on raw genetic data. Only a licensed physician or clinical pharmacist can interpret certified pharmacogenetic panel results and make safe, evidence-based medication adjustments.
Why does my test report list rs4924576 if it is not directly harmful?
Consumer and research microarrays frequently include rs4924576 because it is a common intronic tagging variant. Researchers use tagging variants to track ancestral haplotypes and linkage patterns across the complicated CYP2D6 gene cluster.
What medications rely on the CYP2D6 metabolic pathway?
The CYP2D6 enzyme helps metabolize around 20% of commonly prescribed therapeutic drugs. These include various pain relievers (such as tramadol and codeine), antidepressants, antipsychotics, and beta-blockers used to manage blood pressure.
Sources & further reading
Educational information only, last refreshed 9/7/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Get my report — $29Related variants in CYP2D6
This variant is a key marker for the CYP2D6*10 allele, which results in reduced enzymatic activity and altered metabolism of various psychiatric and analgesic medications.
This variant defines the CYP2D6*4 non-functional allele, which causes impaired metabolism of numerous clinically prescribed medications including antidepressants, tamoxifen, and codeine.
Defines the CYP2D6*17 allele (p.Thr107Ile), which exhibits reduced enzyme activity towards substrates like codeine and certain antidepressants.
Defines the CYP2D6*29 variant (p.Val338Met) conferring decreased metabolic capacity, primarily observed in populations of African descent.
Promoter variant defining the CYP2D6*41 allele, associated with reduced enzyme expression and decreased metabolic capacity for various drugs.
Defines the CYP2D6*6 deletion variant (1707delT) leading to a premature stop codon and loss of enzyme function.