DPYD rs72547533: What Your Genotype Means
The rs72547533 variant is a rare genetic change in the DPYD gene that results in an amino acid substitution known as p.Arg235Trp. This variant is associated with dihydropyrimidine dehydrogenase (DPD) deficiency, which can significantly increase the risk of severe toxicity in patients treated with fluoropyrimidine-based chemotherapy.
What each genotype means
Typical enzyme activity
This genotype represents the most common form of the DPYD gene, which is typically associated with normal dihydropyrimidine dehydrogenase (DPD) enzyme function. Individuals with this genotype are generally expected to process fluoropyrimidine medications, such as 5-fluorouracil or capecitabine, at standard rates. Please discuss your medication plan and any potential side effects with your clinician or pharmacist before starting treatment.
This is the most common genotype found in the general population across all ancestries.
Potential reduced enzyme activity
This genotype includes one copy of the rare c.703C>T (p.Arg235Trp) variant, which may be associated with reduced DPD enzyme activity. Research suggests that individuals carrying such rare DPYD variants may have an increased risk of experiencing severe toxicity when treated with standard doses of fluoropyrimidine chemotherapy. You should discuss this result with your oncologist or pharmacist, as they may consider dose adjustments or alternative therapies.
This genotype is very rare, with the variant allele occurring at a frequency of less than 0.0005 in global populations.
Likely profound enzyme deficiency
This genotype indicates the presence of two copies of the rare c.703C>T variant, which is associated with a high risk of profound dihydropyrimidine dehydrogenase deficiency. Individuals with this profile may be unable to properly break down fluoropyrimidine medications, leading to a significantly increased risk of life-threatening toxicity. It is critical to consult with your healthcare provider or a clinical geneticist to discuss the implications of this result for any potential medical treatment.
This genotype is extremely rare and is not typically observed in standard population databases.
Understanding the rs72547533 Variant
The rs72547533 variant is a specific genetic alteration located within the DPYD gene, which provides instructions for making the enzyme dihydropyrimidine dehydrogenase (DPD). In scientific literature, this variant is often described as c.703C>T, indicating a change in the DNA sequence where a cytosine is replaced by a thymine. This specific change leads to a missense mutation, meaning the protein produced by the gene contains a different amino acid—specifically, arginine is replaced by tryptophan at position 235 (p.Arg235Trp). Because this change occurs in a critical region of the enzyme, it can impair the protein's ability to function correctly. Geneticists classify this as a rare variant, meaning it is not commonly found in the general population, but its potential impact on how the body processes certain medications makes it a subject of interest in the field of pharmacogenomics.
The Role of the DPYD Gene
The DPYD gene is essential for the body's metabolism of pyrimidines, which are the building blocks of DNA and RNA. The DPD enzyme, encoded by this gene, is the rate-limiting step in the catabolism of uracil and thymine. Beyond its natural metabolic role, this enzyme is responsible for breaking down fluoropyrimidine drugs, such as 5-fluorouracil (5-FU) and capecitabine, which are widely used in cancer treatment. When the DPYD gene is functioning normally, the body efficiently clears these drugs from the system. However, if a person carries a deleterious variant that reduces or eliminates DPD enzyme activity, the drugs can accumulate to toxic levels in the blood. This accumulation is the primary cause of severe, and sometimes life-threatening, adverse reactions in patients undergoing chemotherapy, as the body cannot process the medication at standard therapeutic doses.
Clinical Associations and Evidence
Research into rs72547533 has identified it as a likely pathogenic variant linked to dihydropyrimidine dehydrogenase deficiency. Clinical databases, such as ClinVar, have categorized this variant as likely pathogenic based on its potential to disrupt enzyme function. While the evidence strength for this specific variant is currently considered limited compared to more common DPYD variants like *2A or *13, it is recognized as a deleterious mutation. Patients who carry this variant may experience profound toxicity when exposed to fluoropyrimidines, including severe gastrointestinal distress, bone marrow suppression, and neurotoxicity. Because the evidence is still evolving, clinicians are increasingly aware of the need to identify such rare variants in patients before starting chemotherapy. It is important to note that while genetic associations are strong, they are not absolute predictors of clinical outcomes, and individual responses can vary based on other genetic and environmental factors.
Population Frequency
The rs72547533 variant is extremely rare in the general population. According to data from gnomAD, the minor allele frequency (MAF) is less than 0.0005. This rarity means that the vast majority of the global population carries the common, functional version of the gene. Because the variant is so infrequent, it is rarely encountered in routine clinical screening, which often focuses on more prevalent DPYD variants. However, for the small number of individuals who do carry this allele, the clinical implications can be significant. Due to its low frequency, large-scale population studies are difficult to conduct, and much of our current understanding comes from case reports and targeted studies of patients who have already experienced severe adverse drug reactions. As genomic sequencing becomes more accessible, our understanding of the distribution of this variant across different ancestral groups may improve.
Managing Your Genetic Information
If you have received information about your DPYD genotype, it is essential to understand that this is only one piece of a complex health puzzle. You should never use this information to make decisions about your medical care or to interpret your risk for specific conditions without professional guidance. If you are scheduled to undergo chemotherapy, particularly with fluoropyrimidines, discuss your genetic results with your oncologist or a clinical pharmacist. They are trained to interpret these findings in the context of your overall health and can determine if dose adjustments or alternative treatment strategies are necessary to ensure your safety. Genetic testing for pharmacogenomics is a powerful tool for personalized medicine, but it must be integrated into a comprehensive clinical plan managed by your healthcare team to be effective and safe.
How common is this variant?
The rs72547533 variant is a rare deleterious allele with a minor allele frequency of less than 0.0005 in gnomAD, making it uncommon across all major ancestral populations.
Frequently asked questions
What is DPYD deficiency?
DPYD deficiency is a condition where the body lacks enough of the DPD enzyme to properly break down pyrimidines and certain chemotherapy drugs. This can lead to severe, toxic side effects when taking medications like 5-fluorouracil.
Should I get tested for DPYD variants?
Genetic testing for DPYD is typically recommended for patients who are about to start fluoropyrimidine chemotherapy. You should consult your oncologist to see if this testing is appropriate for your specific treatment plan.
Does having a DPYD variant mean I cannot have cancer treatment?
No, having a DPYD variant does not mean you cannot be treated for cancer. It often means your doctor may need to adjust your dosage or choose a different medication to ensure your treatment is safe and effective.
Is rs72547533 the only DPYD variant that matters?
No, there are many known variants in the DPYD gene that can affect enzyme function. Clinicians often screen for a panel of common variants, and rs72547533 is one of many that researchers are studying for clinical relevance.
Sources & further reading
Educational information only, last refreshed 9/16/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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This intronic variant is a marker for reduced DPYD enzyme activity, increasing the risk of severe toxicity from fluoropyrimidine-based chemotherapies.
This variant is linked to decreased dihydropyrimidine dehydrogenase activity, increasing the risk of severe toxicity during fluoropyrimidine chemotherapy.
Defines the DPYD*7 variant (p.Leu311Phe) associated with impaired pyrimidine metabolism and potential fluoropyrimidine toxicity.
Constitutes the DPYD*13 variant (p.Ile560Thr), associated with significantly reduced DPYD enzyme activity and increased risk of severe fluoropyrimidine toxicity.
Also designated as DPYD c.557A>G (p.Tyr186Cys), this variant significantly decreases dihydropyrimidine dehydrogenase activity and predisposes patients to severe fluoropyrimidine toxicity.
Causes the c.2846A>T (p.Asp949Val) missense change in DPYD, associated with reduced enzyme activity and increased risk of fluoropyrimidine-associated toxicity.