F11 rs375422404: Understanding the p.Arg497Ter Variant
The rs375422404 variant in the F11 gene is a genetic change, also known as p.Arg497Ter, that is associated with Factor XI deficiency. This condition can affect the body's ability to form blood clots properly, potentially leading to bleeding issues.
What each genotype means
Typical factor XI levels
This genotype represents the common, non-mutated form of the F11 gene at this position. Individuals with this result do not carry this specific mutation associated with Factor XI deficiency.
This is the most common genotype found in the general population.
Factor XI deficiency carrier
You carry one copy of the p.Arg497Ter mutation, also known as a carrier state for Factor XI deficiency. While carriers typically do not experience severe symptoms, they may have reduced levels of Factor XI protein, which is a protein essential for normal blood clotting.
This genotype is rare in the general population, though carrier status may be more frequent in specific ancestral groups.
Factor XI deficiency
This genotype is associated with Factor XI deficiency, a condition also known as hemophilia C or Rosenthal disease. This condition can lead to impaired blood clotting, which may result in prolonged bleeding after surgery, dental procedures, or trauma; please discuss these results with a healthcare provider or hematologist to understand your personal clinical risk.
This genotype is very rare, with the overall condition estimated to affect approximately 1 in 1 million people worldwide, though it is more common in individuals of Ashkenazi Jewish ancestry.
What is the rs375422404 Variant?
The rs375422404 variant is a specific change in the DNA sequence of the F11 gene, located on the long arm of chromosome 4. In scientific literature, this variant is frequently referred to as c.1489C>T or by its protein-level change, p.Arg497Ter. The 'Ter' notation indicates that this mutation introduces a premature stop codon in the genetic instructions. This effectively tells the cell to stop building the protein prematurely, often resulting in a truncated or non-functional version of the Factor XI protein. Because this variant alters the fundamental structure of the protein, it is categorized as a significant mutation in the context of genetic research. Understanding where this variant sits within the F11 gene helps researchers predict how it might disrupt the normal production of coagulation factors necessary for healthy blood clotting.
The Role of the F11 Gene
The F11 gene provides the instructions for creating the coagulation Factor XI protein. This protein is a vital component of the blood coagulation cascade, which is the complex series of events that allows the body to stop bleeding after an injury. Factor XI circulates in the blood as a zymogen, a precursor that is activated when needed to help form stable blood clots. The protein is structured into several domains, including four 'apple' domains and a catalytic serine protease domain, which work together to facilitate clotting. When the F11 gene contains a pathogenic variant, the resulting Factor XI protein may be produced in insufficient quantities or may not function correctly. This can lead to Factor XI deficiency, a condition historically known as hemophilia C or Rosenthal disease, which is characterized by an impaired ability to form clots.
Research and Clinical Associations
Research into the F11 gene has identified hundreds of variants that can contribute to Factor XI deficiency. The rs375422404 variant is specifically recognized for its potential to disrupt normal protein synthesis. Clinical evidence suggests that individuals carrying this variant may have reduced levels of Factor XI activity. However, the relationship between genetic variants and clinical symptoms is complex. Not everyone with a genetic variant will experience the same severity of bleeding, and some individuals may remain asymptomatic until they undergo a major stressor, such as surgery or dental procedures. The evidence strength for this variant's role in deficiency is considered moderate, reflecting that while the molecular impact is clear, the clinical manifestation can vary significantly between individuals. It is important to note that this information is for educational purposes and does not constitute a medical diagnosis.
Interpreting Your Genetic Information
If you have received information about your status regarding the rs375422404 variant, it is important to understand what this means in a broader context. Genetic testing can identify whether you carry one or two copies of a variant, but it cannot predict the exact clinical outcome or the severity of potential bleeding risks. Because Factor XI deficiency is a complex condition, clinical management is always based on individual health history, blood tests measuring Factor XI activity, and consultation with a healthcare professional. You cannot use this genetic information alone to make medical decisions. If you are concerned about your risk for bleeding disorders or have questions about how this variant might affect your health, you should discuss these results with a doctor, a genetic counselor, or a clinical pharmacist who can provide personalized guidance based on your full medical profile.
How common is this variant?
The rs375422404 variant is considered rare in the general population. Specific frequency data can vary significantly by ancestry and geographic region.
Frequently asked questions
What is Factor XI deficiency?
Factor XI deficiency is an inherited bleeding disorder caused by mutations in the F11 gene. It can lead to abnormal bleeding, particularly after surgery or trauma, though symptoms vary widely.
Is rs375422404 the same as hemophilia C?
Yes, Factor XI deficiency is sometimes referred to as hemophilia C or Rosenthal disease. The rs375422404 variant is one of many genetic changes that can contribute to this condition.
Does having the T allele mean I will have bleeding problems?
Not necessarily. Genetic status is only one factor in determining health. Many people with genetic variants for clotting factors do not experience severe symptoms, and clinical diagnosis requires blood activity testing.
What should I do if I am a carrier of this variant?
If you are a carrier, you should discuss this finding with your healthcare provider. They can help you understand your specific health risks and determine if any precautions are necessary before medical procedures.
Sources & further reading
Educational information only, last refreshed 9/19/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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This deletion variant is associated with hereditary factor XI deficiency, which can lead to increased bleeding risk.
This variant is linked to carrier status for hereditary factor XI deficiency.
This variant in the F11 gene is associated with hereditary factor XI deficiency, a condition that can lead to bleeding disorders.
This SNP is linked to hereditary factor XI deficiency, where carriers may have reduced levels of factor XI protein.
This variant is associated with hereditary factor XI deficiency, with homozygous carriers showing increased clinical risk.
This variant is associated with hereditary factor XI deficiency, a condition that can lead to bleeding disorders.