MEFV rs11571732: Understanding the p.Val726Ala Variant
The rs11571732 variant in the MEFV gene, also known as p.Val726Ala, is a genetic alteration associated with Familial Mediterranean Fever (FMF). It is recognized as a pathogenic variant that can influence carrier status or contribute to the development of inflammatory symptoms.
What each genotype means
Typical MEFV genotype
This genotype represents the most common form of the MEFV gene, where both copies do not carry the V726A variant. Individuals with this profile do not have the specific genetic predisposition associated with this variant for familial Mediterranean fever.
This is the most common genotype observed across all global populations.
MEFV variant carrier
This genotype indicates you carry one copy of the V726A variant in the MEFV gene. While familial Mediterranean fever is typically inherited in an autosomal recessive manner, carrying a single variant may be associated with reduced penetrance or carrier status in certain populations; please discuss any clinical concerns with a healthcare provider.
Carrier frequency for common MEFV variants exceeds 5% in specific populations, including those of Armenian, Arab, and Turkish ancestry.
Potential increased risk profile
This genotype indicates you carry two copies of the V726A variant. This variant is associated with familial Mediterranean fever, an inflammatory condition; however, clinical expression can be variable, and not all individuals with this genotype will develop symptoms. Please consult with a medical professional or genetic counselor to discuss your health history and any necessary clinical evaluation.
This genotype is rare in the general population but is more frequently identified in specific Mediterranean and Middle Eastern populations where the variant is endemic.
What is rs11571732?
The variant rs11571732, commonly referred to as p.Val726Ala, is a specific change in the DNA sequence of the MEFV gene. In this variant, the amino acid valine is replaced by alanine at position 726 of the protein. This change occurs within the 10th exon of the gene, a region frequently analyzed in clinical genetics because it is a hotspot for mutations linked to autoinflammatory conditions. Because this is a missense variant, it alters the primary structure of the resulting protein, which can impact its biological function. Geneticists track this specific location to better understand how individual variations contribute to the risk of developing inflammatory disorders, particularly in populations where this variant is more commonly observed.
The Role of the MEFV Gene
The MEFV gene provides instructions for producing a protein called pyrin, which is primarily expressed in white blood cells. Pyrin plays a critical role in the innate immune system by helping to regulate the inflammatory response. Specifically, it acts as a sensor that helps control the activation of the inflammasome, a complex of proteins that triggers the release of inflammatory cytokines like IL-1β. When the MEFV gene functions correctly, pyrin helps prevent unnecessary or excessive inflammation. However, certain variants in this gene can disrupt the interaction between pyrin and other cellular components, such as caspase-1. This disruption can lead to an overactive inflammatory response, which is the hallmark of conditions like Familial Mediterranean Fever. Understanding this gene is essential for grasping how genetic variations can shift the balance of the immune system.
Research and Clinical Associations
Research has classified the p.Val726Ala variant as pathogenic in the context of Familial Mediterranean Fever. Studies indicate that this mutation can reduce the interaction between the B30.2 domain of pyrin and caspase-1, leading to abnormal inflammasome function and increased inflammatory reactions. While the association with FMF is well-documented, the clinical presentation can be variable. Some individuals carrying this variant may exhibit classic symptoms, while others might show reduced penetrance, meaning they may have milder symptoms or none at all despite having the genetic marker. Because FMF is typically inherited in an autosomal recessive pattern, the presence of this variant in a single copy (carrier status) is often studied in the context of how it might interact with other genetic or environmental factors to influence health outcomes.
Population Frequency
The frequency of the rs11571732 variant varies significantly across different ancestral groups. It is most frequently observed in populations from the Mediterranean and Near East regions. Data from large-scale genomic databases, such as gnomAD, indicate that while the overall global frequency of the C allele is relatively low (approximately 0.2%), it reaches much higher levels in specific populations. In some studies, carrier frequencies in Armenian, Arab, and Turkish populations have been reported to exceed 5%. This higher prevalence is often attributed to historical founder effects and the evolutionary history of these regions. Because of this uneven distribution, the clinical relevance of this variant is often prioritized in genetic screening programs for individuals with ancestry from these specific geographic areas.
Interpreting Your Genetic Information
If you have received information regarding your status for the rs11571732 variant, it is important to understand that genetic markers are only one piece of a complex health puzzle. This information should never be used to self-diagnose or make medical decisions. The presence of a variant does not guarantee the development of a condition, and the absence of a variant does not rule out the possibility of a disease. If you are concerned about your genetic risk or have a family history of inflammatory conditions, the most appropriate step is to consult with a qualified healthcare provider or a genetic counselor. They can help interpret your results in the context of your personal and family medical history. If you are currently taking medications, such as colchicine, always discuss any questions regarding your treatment or dosing with your clinician or pharmacist.
How common is this variant?
The C allele has an overall global frequency of approximately 0.2%, but it is significantly more common in Armenian, Arab, and Turkish populations, where carrier frequencies can exceed 5%.
Frequently asked questions
What is Familial Mediterranean Fever?
Familial Mediterranean Fever is an inherited autoinflammatory disorder characterized by recurrent episodes of fever and painful inflammation in the abdomen, chest, or joints. It is caused by mutations in the MEFV gene, which regulates the body's inflammatory response.
Does having the rs11571732 variant mean I have FMF?
Not necessarily. While this variant is associated with FMF, the condition is typically inherited in an autosomal recessive manner, meaning it usually requires two copies of a pathogenic variant to manifest fully. A genetic counselor can help you understand your specific risk based on your full genetic profile.
Is there a cure for FMF?
There is no cure for FMF, but it is a manageable condition. Medications like colchicine are commonly prescribed to help prevent inflammatory attacks and reduce the risk of long-term complications. Always consult your doctor regarding any treatment plans.
Should I get tested for MEFV variants?
Genetic testing for MEFV variants is typically recommended for individuals who have clinical symptoms of FMF or a strong family history of the condition. You should discuss the necessity and implications of such testing with a healthcare professional.
Sources & further reading
Educational information only, last refreshed 9/28/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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A missense mutation (c.2080A>G, p.Met694Val) in pyrin, a well-established pathogenic variant for familial Mediterranean fever (FMF) with high penetrance.
Missense substitution (c.2079A>G, p.Met694Ile) in MEFV associated with familial Mediterranean fever.
A missense variant (c.2040G>C, p.Met680Ile) in pyrin conferring carrier status for familial Mediterranean fever, widely observed across Eastern Mediterranean cohorts.
A missense substitution (c.2177T>C, p.Val726Ala) in MEFV establishing carrier status for autosomal recessive familial Mediterranean fever, common in Armenian and Arab lineages.
A missense substitution (c.1984G>A, p.Glu66Lys, often referred to as E148Q) associated with reduced penetrance for familial Mediterranean fever.
Carrier variant for Familial Mediterranean Fever (p.Met694Val), conferring carrier status for recurrent autoinflammatory febrile episodes.