CYP2C19 rs72552763: Understanding the *3 Loss-of-Function Variant
The rs72552763 variant, commonly referred to as CYP2C19*3, is a genetic change that results in a non-functional enzyme. This variant is primarily associated with a reduced ability to metabolize certain medications, including the antiplatelet drug clopidogrel and various antidepressants.
What each genotype means
Normal enzyme activity
This genotype represents the functional wild-type state for this specific variant. Individuals with this profile typically possess normal CYP2C19 enzyme activity, which is responsible for metabolizing various medications including clopidogrel and certain antidepressants. Please discuss your medication management and any concerns regarding drug efficacy with your clinician or pharmacist.
This is the most common genotype in most global populations, representing the absence of the loss-of-function *3 allele.
Reduced enzyme activity
Carrying one copy of the A allele (known as the CYP2C19*3 variant) may result in reduced enzyme activity compared to those with two functional copies. This can affect how your body processes medications like clopidogrel, potentially leading to different clinical responses. Please consult your healthcare provider or pharmacist to determine if this genotype is relevant to your current or future medication regimen.
This genotype is observed more frequently in East Asian populations, where the *3 allele is more prevalent, and is considered rare in European populations.
Complete loss of function
This genotype indicates the presence of two copies of the loss-of-function *3 allele, which results in a complete lack of CYP2C19 enzyme activity for this specific variant. This may significantly impact the metabolism of drugs that require this enzyme for activation, such as clopidogrel. It is important to discuss this result with your clinician or pharmacist to ensure your medication plan is appropriate for your genetic profile.
This genotype is rare globally, though it occurs at a higher frequency in East Asian populations compared to other ancestral groups.
What is rs72552763?
The rs72552763 variant is a single nucleotide polymorphism (SNP) located within the CYP2C19 gene. Specifically, it involves a change from guanine to adenine at position 636 (c.636G>A). This specific alteration introduces a premature stop codon, which signals the cell to stop building the protein prematurely. Consequently, the resulting enzyme is truncated and lacks the necessary structure to function correctly. In the nomenclature of pharmacogenetics, this variant is designated as the CYP2C19*3 allele. Because the enzyme produced by this allele is essentially inactive, it is classified as a 'no-function' or 'loss-of-function' variant. Understanding this SNP is important because it directly affects how the body processes specific chemical compounds, including therapeutic drugs that rely on this enzyme for activation or clearance.
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 responsible for the metabolism of a wide array of substances, including hormones and many commonly prescribed medications. For drugs like clopidogrel, the CYP2C19 enzyme acts as a critical 'activator.' Clopidogrel is a prodrug, meaning it must be converted by the liver into its active form to effectively inhibit platelet aggregation and prevent blood clots. When an individual carries the *3 variant, their ability to perform this conversion is significantly impaired. This can lead to lower levels of the active drug in the bloodstream, potentially reducing the medication's effectiveness in preventing cardiovascular events. Beyond clopidogrel, this enzyme also plays a role in metabolizing antidepressants and other drugs, making it a central focus in the field of pharmacogenomics.
Research and Clinical Evidence
Research into rs72552763 has established it as a significant factor in pharmacogenomics, particularly regarding clopidogrel therapy. Clinical studies and meta-analyses have consistently shown that individuals carrying loss-of-function alleles like *3 are at a higher risk of experiencing adverse cardiovascular outcomes when treated with clopidogrel compared to those with normal enzyme function. The evidence strength for this association is considered robust in the context of clinical guidelines, such as those provided by the Clinical Pharmacogenetics Implementation Consortium (CPIC). However, it is important to note that while the association is clear, individual responses to medication are complex and influenced by many factors, including other genetic variants, drug-drug interactions, and lifestyle. Clinicians often use this information to guide therapy choices, such as selecting alternative antiplatelet medications for patients identified as poor metabolizers. Always discuss your genetic results and medication options with your healthcare provider.
Population Frequency
The frequency of the rs72552763 variant varies significantly across different global populations. It is most notable in East Asian ancestries, where the allele frequency typically ranges from 5% to 10%. It is also found at significant frequencies in certain Oceanic populations, sometimes reaching up to 15%. In contrast, the variant is quite rare in European and many other populations, often appearing at frequencies of less than 0.5%. This distribution highlights the importance of considering ancestry when evaluating the potential impact of pharmacogenetic variants. Because the prevalence of the *3 allele is higher in specific groups, the clinical relevance of testing for this variant may be more pronounced in those populations. Genetic testing can help identify whether an individual carries one or two copies of this variant, which helps categorize them into metabolizer phenotypes such as intermediate or poor metabolizers.
What You Can Do With This Information
If you have information about your CYP2C19 genotype, the most important step is to share it with your doctor or pharmacist. This information is a tool for precision medicine, allowing healthcare providers to make more informed decisions about your treatment plan. If you are prescribed a medication known to be metabolized by CYP2C19, such as clopidogrel, your clinician can use your genotype to determine if a standard dose is appropriate or if an alternative medication might be safer and more effective for you. You cannot use this information to diagnose yourself or to make changes to your prescribed medications on your own. Never stop or alter your medication regimen without professional medical guidance. Genetic testing provides a piece of the puzzle, but your clinician will integrate this with your full medical history, current health status, and other clinical factors to provide the best possible care.
How common is this variant?
The rs72552763 variant is significant in East Asian ancestries with a 5-10% allele frequency, while it remains rare in European populations at less than 0.5%.
Frequently asked questions
Does having the rs72552763 variant mean I cannot take clopidogrel?
Not necessarily. While the variant affects how your body processes the drug, your doctor will consider your overall health and clinical needs to decide if clopidogrel is the right choice or if an alternative medication is better suited for you.
Is rs72552763 the only variant that affects CYP2C19?
No, there are several other variants in the CYP2C19 gene, such as *2, that also affect enzyme function. Genetic testing often looks at a panel of these variants to determine your overall metabolizer status.
Can I change my CYP2C19 genotype?
No, your genotype is determined by the DNA you inherited from your parents and cannot be changed. However, knowing your genotype allows your healthcare team to adjust your medical care accordingly.
Where can I get tested for this variant?
Clinical genetic testing is typically ordered by a healthcare provider if it is relevant to your treatment. You should consult with your doctor or a genetic counselor to discuss whether testing is appropriate for your specific medical situation.
Sources & further reading
Educational information only, last refreshed 9/20/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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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.
Defines the CYP2C19*4 allele caused by an ATG start codon alteration that abolishes translation, resulting in reduced or absent drug metabolism capacity.