CYP2D6 rs28371723: Understanding the *41 Variant
The rs28371723 variant is a specific genetic change located within the CYP2D6 gene, which plays a critical role in how the body processes many common medications. This variant is a defining component of the CYP2D6*41 allele, which is associated with decreased enzyme function and intermediate drug metabolism.
What each genotype means
Normal enzyme activity
This genotype represents the wild-type or reference state for this specific variant, meaning you do not carry the CYP2D6*41 decreased-function allele at this position. Your enzyme activity is expected to be normal, assuming no other variants are present. Please discuss any concerns regarding medication response with your clinician or pharmacist.
This is the most common genotype, found in the majority of individuals across most global populations.
Reduced enzyme activity
You carry one copy of the CYP2D6*41 variant, which is associated with decreased enzyme function. This may result in an intermediate metabolizer status, potentially affecting how your body processes certain medications. Please consult your healthcare provider or pharmacist to determine if your medication dosing requires adjustment based on this genetic profile.
Carried by approximately 15-20% of people in European and Middle Eastern populations, where this variant is most prevalent.
Significantly reduced enzyme activity
You carry two copies of the CYP2D6*41 variant, which is linked to reduced CYP2D6 enzyme activity. This genotype is often categorized as an intermediate metabolizer, which may lead to slower processing of specific drugs metabolized by this enzyme. You should discuss this result with your clinician or pharmacist to ensure your current or future medication dosages are appropriate for your metabolism.
This genotype is less common than the heterozygous state, occurring in a smaller percentage of individuals within European and Middle Eastern cohorts.
What is rs28371723?
The rs28371723 variant is a single nucleotide polymorphism (SNP) located in the CYP2D6 gene. Specifically, it is identified as the c.985+39G>A variant, situated within an intron of the gene. In the context of pharmacogenomics, this SNP is a key marker used to define the CYP2D6*41 haplotype. The CYP2D6 gene provides instructions for making an enzyme that is responsible for metabolizing approximately 25% of clinically used drugs, including antidepressants, antipsychotics, and certain pain medications. Because this variant is located in a non-coding region (an intron), it does not change the protein sequence directly, but it is known to influence the expression or splicing of the gene, ultimately leading to reduced enzyme activity. Genetic testing for this variant is often part of broader panels designed to assess an individual's metabolic profile.
The Role of CYP2D6 in Drug Metabolism
The CYP2D6 enzyme is a member of the cytochrome P450 family, a group of enzymes primarily found in the liver that break down foreign substances, including drugs. Individuals are categorized into different metabolizer statuses based on their CYP2D6 genotype: poor, intermediate, normal, or ultrarapid metabolizers. The *41 allele, which carries the rs28371723 variant, is classified by the Clinical Pharmacogenetics Implementation Consortium (CPIC) as a decreased-function allele. When an individual carries this allele, their ability to process certain medications may be slower than those with normal-function alleles. This can lead to higher-than-expected levels of a drug in the bloodstream if the drug is metabolized by CYP2D6, or reduced effectiveness if the drug requires activation by the enzyme. Understanding these variations helps clinicians tailor medication choices and dosages to an individual's genetic profile.
Research and Clinical Evidence
Research into rs28371723 and the *41 allele is categorized as having limited to moderate evidence strength in some clinical contexts, though it is widely recognized in pharmacogenomic guidelines. Studies have consistently associated the *41 allele with intermediate metabolizer status. Because CYP2D6 is highly polymorphic, the clinical impact of this variant often depends on the other allele present on the second copy of the gene. For example, an individual with one *41 allele and one non-functional allele may be classified as a poor metabolizer, whereas someone with one *41 allele and one normal-function allele may be an intermediate metabolizer. While the association between this variant and altered drug metabolism is well-documented in scientific literature, the clinical significance varies by specific drug. Always consult with a healthcare provider or pharmacist to interpret how your specific genetic results might influence your response to a particular medication.
Population Frequency
The frequency of the CYP2D6*41 allele, and by extension the rs28371723 variant, varies significantly across different global populations. In European cohorts, the minor allele frequency is typically observed between 0.08 and 0.12. The variant is notably more common in Middle Eastern populations, where frequencies ranging from 0.15 to 0.20 have been reported in various studies. These differences highlight the importance of considering ancestry when interpreting pharmacogenetic data. Because this variant is relatively common in these regions, it is a significant contributor to the prevalence of the intermediate metabolizer phenotype in these populations. Genetic diversity in the CYP2D6 gene remains a major area of study, as researchers continue to identify how these frequency patterns influence public health and personalized medicine strategies globally.
What You Can Do With This Information
If you have received genetic testing results indicating the presence of the rs28371723 variant, it is important to view this information as a tool for communication with your healthcare team. This result does not provide a diagnosis or a definitive prediction of how you will react to every medication. Instead, it provides data that your doctor or pharmacist can use to optimize your treatment plan. You should never change or stop taking prescribed medications based on genetic test results without professional medical guidance. If you are concerned about how your genetics might affect your drug response, bring your report to your next appointment. Your clinician can use established guidelines, such as those provided by CPIC, to determine if a dosage adjustment or an alternative medication is appropriate for your specific genetic profile.
How common is this variant?
The rs28371723 variant is found at a frequency of approximately 0.08-0.12 in European populations and 0.15-0.20 in Middle Eastern cohorts.
Frequently asked questions
Does having the rs28371723 variant mean I am a poor metabolizer?
Not necessarily. Being a poor metabolizer usually depends on the combination of both copies of your CYP2D6 gene; having this variant often classifies you as an intermediate metabolizer, but your overall status depends on your other allele.
Should I change my medication if I have this variant?
No, you should never change your medication without consulting your doctor. Genetic results are only one piece of the puzzle, and your clinician must consider your overall health and other factors before making changes.
Is this variant the same as CYP2D6*41?
Yes, the rs28371723 variant is a defining genetic marker used to identify the CYP2D6*41 allele. It is one of the specific changes that researchers look for to confirm the presence of this haplotype.
Where can I find more information on how this affects specific drugs?
You can visit the Clinical Pharmacogenetics Implementation Consortium (CPIC) website or PharmGKB. These resources provide evidence-based guidelines on how specific CYP2D6 genotypes influence the dosing of various medications.
Sources & further reading
Educational information only, last refreshed 9/14/2026. 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.