CYP2C19 rs28399504: Understanding the *4 Variant
The rs28399504 variant is a specific genetic change located within the CYP2C19 gene. It is associated with the CYP2C19*4 allele, which can lead to reduced or absent drug metabolism capacity in affected individuals.
What each genotype means
Normal enzyme activity
This genotype represents the typical, fully functional version of the CYP2C19 gene, often referred to as the *1 allele. Individuals with this profile generally possess standard capacity to metabolize medications processed by this enzyme. Please discuss any medication-related concerns or dosing questions with your clinician or pharmacist.
This is the most common genotype found across all global populations.
Reduced enzyme activity
This genotype indicates you carry one copy of the CYP2C19*4 variant, which is associated with reduced or absent enzyme function. You may be considered an intermediate metabolizer of certain drugs, which can influence how your body processes medications like clopidogrel or omeprazole. Please consult your healthcare provider or pharmacist to determine if this impacts your specific treatment plan.
This genotype is rare globally, with the minor allele frequency typically observed below 0.5% across most populations.
Poor enzyme activity
This genotype indicates you carry two copies of the CYP2C19*4 variant, which is known to abolish translation of the enzyme, resulting in a poor metabolizer status. This may significantly alter the effectiveness or safety of medications that rely on this enzyme for processing. It is important to discuss this result with your doctor or pharmacist before starting or adjusting any medications.
This genotype is extremely rare in the general population.
What is rs28399504?
The rs28399504 variant is a single nucleotide polymorphism (SNP) located on chromosome 10. In the context of the CYP2C19 gene, this specific change is often referred to as a start codon alteration. Specifically, it involves a change at the initiation codon (c.1A>G) that prevents the proper translation of the genetic code into a functional protein. Because this variant disrupts the very beginning of the protein-building process, the resulting enzyme is typically non-functional. This makes rs28399504 a significant marker for researchers studying how genetic variations influence the body's ability to process medications.
The Role of the CYP2C19 Gene
The CYP2C19 gene provides the instructions for creating an enzyme that belongs to the cytochrome P450 family. These enzymes are primarily found in the liver and are essential for metabolizing, or breaking down, a wide variety of substances, including many commonly prescribed medications. When the CYP2C19 enzyme functions normally, it helps clear drugs from the body at an expected rate. However, when genetic variants like rs28399504 result in a loss of function, the body may struggle to process these drugs effectively. This can lead to altered drug levels in the bloodstream, which may impact how well a medication works or increase the risk of side effects.
Research and Clinical Associations
Scientific research has linked the CYP2C19*4 allele, defined by this variant, to a 'poor metabolizer' phenotype. Studies have investigated its impact on the metabolism of various drugs, including anti-ulcer medications like omeprazole and antiplatelet agents like clopidogrel. While the evidence strongly supports the role of this variant in reducing enzyme activity, the clinical implications can vary depending on the specific drug and the individual's overall genetic profile. Because pharmacogenomics is a complex field, researchers emphasize that having this variant does not automatically predict a specific clinical outcome for every patient. The strength of evidence for this variant is considered limited in some contexts, and clinicians often look at a patient's entire diplotype—the combination of alleles inherited from both parents—to make informed decisions.
What You Can and Cannot Do
It is important to understand that genetic information is only one piece of the puzzle when it comes to your health. You cannot use this information to diagnose yourself or to make changes to your prescribed medications. If you have received results indicating you carry this variant, the most important step is to discuss these findings with your healthcare provider or a pharmacist. They are trained to interpret how your specific genetic makeup might interact with your current or future treatments. They can help determine if a dosage adjustment or an alternative medication is appropriate for your specific situation. Never stop or change your medication regimen based on genetic test results without professional medical guidance.
How common is this variant?
The rs28399504 variant is rare globally, with a minor allele frequency generally reported below 0.5% across most major population groups.
Frequently asked questions
What does it mean to be a poor metabolizer?
A poor metabolizer has a reduced ability to break down certain drugs due to genetic variations in enzymes like CYP2C19. This can cause medications to stay in the system longer than intended, potentially increasing the risk of side effects.
Does having the rs28399504 variant mean my medication won't work?
Not necessarily. While this variant affects how the body processes certain drugs, the clinical impact depends on the specific medication and your overall genetic profile. Always consult your doctor to understand how this applies to your specific prescriptions.
Should I get tested for CYP2C19 variants?
Genetic testing for pharmacogenomics is typically recommended by healthcare providers when starting specific medications that are known to be affected by these genes. You should discuss the necessity of such testing with your clinician.
Can I change my diet to fix my CYP2C19 metabolism?
No, genetic variants like rs28399504 are inherited and cannot be changed by diet or lifestyle modifications. These variants affect the production of enzymes in your liver, which is determined by your DNA.
Sources & further reading
Educational information only, last refreshed 9/28/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs28399504?
Upload a raw DNA file from 23andMe, AncestryDNA, MyHeritage, or FamilyTreeDNA and see this variant — plus thousands more — interpreted in your full report.
Get my report — $29Related variants in CYP2C19
Defines the CYP2C19*17 increased function allele, conferring rapid or ultrarapid metabolism for CPIC-actionable drugs including clopidogrel, PPIs, and SSRIs.
The CYP2C19*2 loss-of-function splicing defect results in impaired biotransformation of prodrugs including clopidogrel and altered clearance of proton pump inhibitors and select antidepressants.
Variant in the CYP2C19 locus associated with altered metabolism of clopidogrel and proton-pump inhibitors.
Defines the CYP2C19*8 loss-of-function variant (c.358T>C, p.Trp120Arg) which results in no enzymatic activity and impaired metabolism of CYP2C19 substrates.
Defines the non-functional CYP2C19*3 null allele resulting from a premature stop codon, leading to poor metabolism of drugs such as clopidogrel, escitalopram, and proton pump inhibitors.
Known as CYP2C19*3, this premature stop codon (c.636G>A, p.Trp212Ter) results in a complete loss-of-function phenotype for clopidogrel and antidepressant metabolism.