CYP2C9 rs375406404: Understanding This Rare Genetic Variant
The rs375406404 variant is a rare genetic change located within the CYP2C9 gene, which is essential for processing many common medications. This variant is associated with potential alterations in enzyme function, which may influence how an individual metabolizes specific drugs.
What each genotype means
Typical CYP2C9 enzyme activity
This genotype represents the most common genetic state for this position in the CYP2C9 gene. Research suggests individuals with this profile typically exhibit standard enzyme function for metabolizing medications processed by CYP2C9. Please discuss any medication dosing or potential drug interactions with your clinician or pharmacist.
This is the most common genotype observed across all global populations.
Rare variant carrier
You carry one copy of the rare T allele at this position, which may result in a V to L or V to M amino acid substitution in the CYP2C9 enzyme. Because this is a rare variant, the clinical impact on drug metabolism is currently limited and not fully established in scientific literature. Please consult with your healthcare provider or a pharmacist regarding how this might influence your response to specific medications.
This genotype is rare and found at very low frequencies in global population databases.
Rare variant homozygous
You carry two copies of the rare T allele at this position. While this variant is predicted to alter the structure of the CYP2C9 enzyme, there is limited clinical evidence regarding the specific functional consequences of this homozygous state. You should discuss this finding with your clinician or pharmacist to determine if it has any relevance to your current or future medication management.
This genotype is extremely rare and is observed in a negligible fraction of the global population.
What is the rs375406404 Variant?
The rs375406404 variant is a specific change in the DNA sequence of the CYP2C9 gene. In genetics, a single nucleotide polymorphism (SNP) like this represents a variation at a single position in the genome. This particular variant is categorized as a non-synonymous substitution, meaning it results in an amino acid change within the protein structure of the CYP2C9 enzyme. Specifically, it leads to a valine-to-leucine or valine-to-methionine substitution. Because this variant is rare, it is not as extensively studied as more common variants like CYP2C9*2 or *3. Its presence suggests a potential change in the enzyme's ability to perform its normal biological tasks, though the exact functional impact of this specific change is still being characterized by the scientific community.
The Role of the CYP2C9 Gene
The CYP2C9 gene provides instructions for making an enzyme that belongs to the cytochrome P450 family. These enzymes are primarily found in the liver and are responsible for the metabolism of a wide array of substances, including many clinically important drugs. CYP2C9 is particularly significant because it helps break down medications such as warfarin, phenytoin, various non-steroidal anti-inflammatory drugs (NSAIDs), and certain anti-diabetic agents. By converting these drugs into forms that the body can easily eliminate, the CYP2C9 enzyme plays a critical role in determining how long a medication stays in the system and how effective it is. Variations in this gene can lead to differences in enzyme activity, which may result in either faster or slower drug metabolism compared to the average population.
Research and Evidence Strength
Current research into rs375406404 is limited, and its clinical significance is not yet fully established. While the CYP2C9 gene itself is a well-documented pharmacogene with clear guidelines for common variants, rare variants like rs375406404 often lack the large-scale clinical data required to definitively predict drug response. Most existing studies on CYP2C9 focus on well-known star alleles that have clear, measurable effects on drug clearance. Because rs375406404 is rare, it has not been the primary subject of large-scale genome-wide association studies (GWAS) that typically confirm clinical impact. Consequently, while the variant is known to alter the protein sequence, its specific influence on the safety or efficacy of any particular medication remains an area of ongoing investigation rather than a settled clinical fact.
Population Frequency
The rs375406404 variant is classified as rare across global populations. Unlike common variants that may appear in 10% to 20% of certain ancestral groups, this specific SNP is found at very low frequencies. Because of its rarity, it is difficult to establish clear patterns of distribution across different ethnicities or geographic regions. Most population databases indicate that the vast majority of individuals do not carry this specific variant. When a variant is this uncommon, it is often identified only in small subsets of individuals, making it challenging for researchers to gather enough data to draw broad conclusions about its prevalence or its specific impact on health outcomes across diverse human populations.
What You Can Do With This Information
If you have received information about the rs375406404 variant, it is important to understand that this is a research-level finding rather than a diagnostic result. Because the evidence for this variant is limited, it should not be used to make independent decisions about your health or medication regimen. Genetic information is complex, and drug metabolism is influenced by many factors, including other genes, age, diet, and other medications you may be taking. If you are concerned about how your body processes a specific drug, the best course of action is to consult with your physician or a clinical pharmacist. They can interpret your genetic data in the context of your overall health history and provide guidance on whether any adjustments to your treatment plan are necessary.
How common is this variant?
The rs375406404 variant is considered rare across all major population groups, with very low frequency observed in global genetic databases.
Frequently asked questions
What does it mean if I have a rare CYP2C9 variant?
Having a rare variant means your DNA sequence differs from the most common version at that specific location. Because it is rare, scientists may not yet have enough data to know exactly how it affects your health or drug metabolism.
Should I change my medication based on this result?
No. You should never change your medication or dosage based on genetic test results without speaking to your doctor. Only a healthcare professional can determine if your genetic profile is relevant to your specific treatment plan.
Is CYP2C9 testing standard for everyone?
CYP2C9 testing is typically performed only when a doctor needs to understand how a patient might metabolize specific drugs, such as warfarin. It is not a routine test for the general population.
Where can I find more information about my specific variant?
You can search for your rsID on databases like ClinVar or the Pharmacogene Variation Consortium (PharmVar). These sites provide the most current scientific understanding of specific genetic variants.
Sources & further reading
Educational information only, last refreshed 9/26/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Get my report — $29Related variants in CYP2C9
Coding variant conferring the CYP2C9*4 allele with decreased enzymatic activity affecting clearance of drugs such as warfarin and phenytoin.
Missense mutation defining the CYP2C9*5 allele that dramatically lowers metabolic activity towards oral anticoagulants and anti-epileptic medications.
A rare variant in the CYP2C9 gene that may impact the metabolism of various clinical drugs.
Defining the CYP2C9*3 (p.Ile359Leu) allele, this variant markedly decreases enzymatic activity, requiring reduced dosages for warfarin and phenytoin to prevent toxicity.
The CYP2C9*3 allele significantly reduces enzyme activity, necessitating dose adjustments for drugs like warfarin and phenytoin to avoid toxicity.
The CYP2C9*2 variant results in reduced enzymatic activity, which is a critical factor in determining appropriate dosing for warfarin and other substrates.