CYP2D6 rs72558188: Understanding the *21 Non-Functional Allele
The rs72558188 variant is a specific genetic marker located within the CYP2D6 gene. It serves as a defining component of the CYP2D6*21 allele, which is associated with a complete loss of enzyme activity.
What each genotype means
Normal CYP2D6 function baseline
You carry two copies of the reference sequence at this position, meaning you do not carry the specific frameshift variant defining the non-functional CYP2D6*21 allele. Overall CYP2D6 enzyme activity depends on your complete diplotype across all tested variants and copy number changes. Consult your physician or pharmacist regarding how your overall metabolizer status affects medication selection and dosing.
Carried by more than 99.8% of individuals globally across all major ancestral populations.
Reduced enzyme activity carrier
You carry one copy of the insertion/frameshift variant defining the non-functional CYP2D6*21 allele alongside one reference allele. Because this variant disrupts the CYP2D6 reading frame and abolishes activity from this copy, your overall metabolic capacity may be reduced to an intermediate metabolizer phenotype depending on your second allele. Always discuss your personal medication dosing and pharmacogenomic profile with a clinician or pharmacist before altering drug therapy.
Extremely rare globally (frequency <0.1%), predominantly observed in East Asian cohorts.
Significantly impaired enzyme activity
You carry two copies of the non-functional frameshift variant defining the CYP2D6*21 allele, indicating a lack of functional CYP2D6 enzyme activity from this locus. In pharmacogenomic research, individuals with two null alleles are categorized as poor metabolizers, which can alter therapeutic response and increase adverse effect risks for CYP2D6-metabolized drugs. You should share these results with your healthcare provider or clinical pharmacist to guide safe medication selection and dosing.
Exceptionally rare across all worldwide populations, with predicted carrier rates well below 0.01%.
What is rs72558188?
The rs72558188 variant is a single nucleotide polymorphism (SNP) found within the CYP2D6 gene, a highly complex and polymorphic region of the human genome. In the context of pharmacogenomics, this specific SNP is recognized as a key defining marker for the CYP2D6*21 allele. This allele is characterized by a frameshift mutation, which disrupts the normal reading frame of the genetic code. Because of this disruption, the body is unable to produce a functional version of the CYP2D6 enzyme from this specific genetic template. When an individual carries this allele, the enzyme's ability to process or metabolize certain substances is effectively abolished. Understanding such variants is a primary focus of pharmacogenomics, as they help explain why individuals may process medications at vastly different rates, potentially impacting both the safety and the efficacy of various clinical treatments.
The Role of the CYP2D6 Gene
The CYP2D6 gene provides instructions for making an enzyme called cytochrome P450 2D6. This enzyme is part of the cytochrome P450 system, a group of proteins primarily found in the liver that are responsible for breaking down, or metabolizing, a wide array of foreign substances, including approximately 20% of commonly prescribed medications. These include drugs used in psychiatry, pain management, oncology, and cardiology. Because the CYP2D6 gene is highly polymorphic—meaning it contains many natural variations—the activity of the resulting enzyme can range from completely absent to significantly increased. When a variant like rs72558188 leads to a non-functional enzyme, the body may struggle to clear certain drugs from the system, or it may fail to activate "prodrugs" that require the enzyme to become effective. This variability is a cornerstone of personalized medicine, as it highlights the importance of genetic factors in determining how a patient responds to standard drug dosages.
Research and Clinical Evidence
The evidence linking rs72558188 to the CYP2D6*21 allele and subsequent loss of enzyme function is well-documented in genetic databases, though it is categorized as having limited clinical evidence regarding its broad impact on specific drug outcomes compared to more common variants. Research indicates that this variant is a structural component of the *21 allele, which is classified by the Clinical Pharmacogenetics Implementation Consortium (CPIC) as a non-functional allele. While the association between the genotype and the loss of enzymatic activity is scientifically established, the clinical implications depend heavily on the other allele an individual carries. If a person has one non-functional allele and one normal-function allele, their overall metabolism may remain within a normal range. However, if both alleles are non-functional, the individual may be classified as a poor metabolizer. Patients should always consult with their clinician or pharmacist to interpret how their specific genetic profile might influence their response to prescribed medications.
Population Frequency and Distribution
The rs72558188 variant is considered rare on a global scale. According to data from the Genome Aggregation Database (gnomAD), the minor allele frequency is generally reported as less than 0.001. Documentation of this variant is predominantly found in East Asian cohorts, where it has been identified as part of the genetic landscape of the region. Because of its rarity, it is not typically included in standard, broad-spectrum pharmacogenetic screening panels unless those panels are specifically designed to capture a comprehensive range of rare CYP2D6 alleles. The distribution of such variants underscores the importance of considering ancestral background in genetic research, as the prevalence of specific alleles can vary significantly between different global populations. As sequencing technologies become more accessible, our understanding of these rare variants continues to grow, providing a more nuanced picture of human genetic diversity and its role in drug metabolism.
Navigating Your Genetic Information
Information about variants like rs72558188 is intended for educational purposes and should not be used to make independent medical decisions. If you have received genetic testing results indicating the presence of this variant, it is important to understand that a single SNP does not provide a complete picture of your metabolic phenotype. Pharmacogenomics is a complex field where the interaction between multiple genes, environmental factors, and lifestyle choices determines how your body processes drugs. You cannot use this information to diagnose a condition or to adjust your medication dosage on your own. If you are concerned about how your genetics might affect your treatment, bring your report to your healthcare provider or a clinical pharmacist. They are trained to interpret these results in the context of your overall health history and can provide guidance on whether a medication adjustment or alternative therapy is appropriate for your specific needs.
How common is this variant?
The rs72558188 variant is rare globally, with a minor allele frequency of less than 0.001 in gnomAD, and is primarily documented in East Asian cohorts.
Frequently asked questions
What does it mean to be a 'poor metabolizer' for CYP2D6?
A poor metabolizer has little to no functional CYP2D6 enzyme activity. This can lead to higher levels of certain drugs in the blood, increasing the risk of side effects, or reduced effectiveness of drugs that need the enzyme to be activated.
Is rs72558188 tested in standard genetic panels?
Because rs72558188 is a rare variant, it is not included in all standard pharmacogenetic panels. Many clinical tests focus on the most common variants, so you should check with your testing provider to see if this specific SNP was included in your report.
Can I change my medication based on this result?
No. You should never change your medication or dosage based on genetic test results without consulting your doctor. Only a healthcare professional can determine if your genetic profile requires a change in your treatment plan.
Why is CYP2D6 so important in medicine?
CYP2D6 is responsible for metabolizing about 20% of commonly used drugs, including many antidepressants, antipsychotics, and pain medications. Because it is highly variable between people, it is a major focus for predicting how patients will respond to these treatments.
Sources & further reading
Educational information only, last refreshed 10/17/2026. 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 non-functional CYP2D6*41 splice defect associated with intermediate metabolizer phenotype affecting codeine, tamoxifen, and SSRI metabolism.