CYP2D6 rs28371764: Understanding the *17 Allele and Drug Metabolism
The rs28371764 variant is a specific genetic change within the CYP2D6 gene that defines the *17 allele. This variant is associated with reduced enzyme activity, which can influence how an individual's body processes certain medications.
What each genotype means
Normal enzyme activity
This genotype represents the presence of two functional copies of the CYP2D6 gene, often referred to as the *1 allele. Individuals with this profile typically exhibit standard metabolism for medications processed by the CYP2D6 enzyme. Please discuss any medication dosing or concerns with your clinician or pharmacist.
This is the most common genotype globally, though its frequency varies significantly across different ancestral populations.
Reduced enzyme activity
This genotype indicates you carry one copy of the reduced-function *17 allele (p.Thr107Ile) alongside one functional copy. Research suggests this may lead to slower metabolism of certain substrates, such as codeine or specific antidepressants, particularly in individuals of African ancestry. Please consult your healthcare provider or pharmacist regarding how this may influence your response to specific medications.
This genotype is most frequently observed in individuals of African and African American ancestry, with a combined minor allele frequency for the *17 variant typically ranging between 15% and 25% in these groups.
Significantly reduced enzyme activity
This genotype indicates you carry two copies of the reduced-function *17 allele. This configuration is associated with a more pronounced reduction in CYP2D6 enzyme activity compared to individuals with one functional copy. You should discuss the potential for altered drug metabolism with your clinician or pharmacist before starting any medication known to be processed by this enzyme.
This genotype is rare and primarily found in populations of African descent, reflecting the specific distribution of the *17 allele.
What is the rs28371764 Variant?
The rs28371764 variant is a single nucleotide polymorphism (SNP) located within the CYP2D6 gene. In the scientific community, this specific genetic change is the defining marker for the CYP2D6*17 allele. The variant results in a change in the amino acid sequence of the resulting protein, specifically a substitution of threonine to isoleucine at position 107 (p.Thr107Ile). This structural change is significant because it alters the function of the CYP2D6 enzyme, which is a critical protein involved in the metabolism of many common drugs. Because this variant is part of a complex gene known for high levels of genetic diversity, it is often studied alongside other variations to determine an individual's overall metabolic profile.
The Role of the CYP2D6 Gene
The CYP2D6 gene provides instructions for making an enzyme that belongs to the cytochrome P450 family. These enzymes are primarily responsible for detoxifying or activating a wide range of substances, including approximately 20-25% of all clinically used medications. The CYP2D6 enzyme is particularly important for processing antidepressants, antipsychotics, and certain pain medications like codeine. Because the gene is highly polymorphic, meaning it has many different versions or 'alleles,' people can have very different levels of enzyme activity. Some individuals have normal function, while others may have reduced or completely absent activity. Understanding these variations is a core component of pharmacogenomics, a field that seeks to tailor medical treatments to an individual's unique genetic makeup to improve efficacy and reduce the risk of adverse drug reactions.
Research and Clinical Associations
Research has consistently categorized the CYP2D6*17 allele, defined by rs28371764, as a 'reduced-function' allele. In laboratory studies, the enzyme produced by this allele shows decreased intrinsic clearance of substrates like bufuralol compared to the normal-functioning *1 allele. Because of this reduced activity, individuals carrying this variant may metabolize certain drugs more slowly than others. While the evidence for this functional impact is well-documented in vitro, the clinical implications can be complex. Factors such as other genetic variants, drug-drug interactions, and environmental influences also play a role in how a person responds to medication. Consequently, the evidence strength for specific clinical outcomes remains limited, and researchers emphasize that genetic testing is only one piece of the puzzle when determining appropriate drug dosages.
Population Frequency
The frequency of the rs28371764 variant varies significantly across different global populations. It is most commonly observed in individuals of African ancestry, where the *17 allele frequency is estimated to be between 15% and 25% in many studies. In contrast, this variant is considered rare or absent in many other ethnic groups, such as those of European or East Asian descent. This disparity highlights the importance of considering ancestry in pharmacogenomic research, as the prevalence of specific alleles can dictate which genetic tests are most relevant for different populations. Because of this uneven distribution, clinicians working with diverse patient populations must be aware of the specific genetic markers that are most common within those groups to provide the most accurate personalized care.
What You Can Do With This Information
If you have received genetic testing results indicating the presence of the rs28371764 variant, it is important to understand that this is not a medical diagnosis. This information simply describes a variation in your genetic code that may influence how your body processes certain medications. You should never make changes to your prescribed medications or dosages based on this information alone. Instead, use these results as a tool to facilitate a conversation with your healthcare provider or a clinical pharmacist. They can interpret your genetic profile in the context of your overall health, current medications, and medical history. By discussing your genotype with a professional, you can work together to ensure that your treatment plan is safe, effective, and tailored to your specific needs.
How common is this variant?
The rs28371764 variant is common in African and African American populations with a minor allele frequency of approximately 15-25%, while it is rare in other global populations.
Frequently asked questions
Does having the rs28371764 variant mean I cannot take certain medications?
Not necessarily. This variant is associated with reduced enzyme activity, which might mean your body processes certain drugs more slowly. Your doctor can use this information to adjust your dosage or choose an alternative medication if needed.
Is rs28371764 the same as CYP2D6*17?
Yes, the rs28371764 SNP is the defining genetic marker for the CYP2D6*17 allele. When you see *17 in a report, it is referring to the presence of this specific genetic change.
Should I get tested for this variant?
Genetic testing for CYP2D6 is typically ordered by a healthcare provider when there is a clinical need to understand how a patient might respond to a specific medication. You should discuss the necessity of such testing with your doctor.
Can I change my medication based on my genotype?
No. You should never change your medication or dosage without consulting your healthcare provider. Genetic information is only one factor in determining the best treatment plan for you.
Sources & further reading
Educational information only, last refreshed 9/29/2026. 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*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.
Defines the non-functional CYP2D6*41 splice defect associated with intermediate metabolizer phenotype affecting codeine, tamoxifen, and SSRI metabolism.