F5 rs3948464: What Your Genotype Means
The rs3948464 polymorphism is a common single nucleotide variation situated in the coagulation factor V (F5) gene. Although the F5 gene is famous for harboring major thrombophilia risk alleles such as Factor V Leiden, rs3948464 is cataloged as a benign background variation. It is widely evaluated during genetic panel sequencing for coagulation pathways and displays no established independent risk for cardiovascular disease or bleeding disorders.
What each genotype means
Common genetic profile
This genotype represents the most frequently observed sequence at this position in the F5 gene. Research indicates this variant is considered benign and is commonly analyzed in coagulation factor V panels without specific clinical implications for clotting risk.
This is a common genotype found across most global populations.
Common genetic profile
Carrying one copy of the T allele at this position is a frequent observation in the general population. Current evidence classifies this variant as benign, and it is not associated with significant changes in coagulation factor V function or clinical disease risk.
This heterozygous genotype is common, appearing in a significant portion of the worldwide population.
Common genetic profile
This genotype represents the alternative homozygous state for this variant. It is widely documented as a benign polymorphism in the F5 gene and does not carry known clinical significance regarding blood coagulation or health predispositions.
This genotype is observed frequently across diverse ancestral groups.
Genomic Context and Molecular Characteristics
The rs3948464 variant is a single nucleotide polymorphism located within the coding sequence of the human coagulation factor V (F5) gene on chromosome 1q24.2. In genomic sequencing data and public repositories such as [NCBI dbSNP](https://www.ncbi.nlm.nih.gov/snp/rs3948464), this locus involves a common nucleotide substitution, frequently tracked with C and T alleles on standard reporting strands. Because it falls within a gene closely tied to hemostatic balance, rs3948464 is regularly captured whenever clinical assays run comprehensive panels or targeted sequencing across the factor V locus. However, unlike pathogenic missense mutations that destabilize protein conformation or eliminate critical enzymatic cleavage boundaries, rs3948464 represents normal human sequence variation. Modern clinical evaluation frameworks routinely identify it as a benign polymorphism that does not compromise standard transcription or translation processes.
The Biological Function of the F5 Gene
The F5 gene encodes coagulation factor V, a high-molecular-weight plasma glycoprotein synthesized predominantly by hepatocytes and megakaryocytes as described in [MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/f5/). Factor V circulates as an inactive procofactor until it undergoes proteolytic activation by thrombin or activated factor X (Factor Xa). Once activated, factor Va associates with factor Xa, calcium, and acidic phospholipids on membrane surfaces to form the prothrombinase complex, which accelerates the conversion of prothrombin into active thrombin by orders of magnitude. The activity of factor Va is tightly counterbalanced by the anticoagulant pathway, wherein activated protein C (APC) proteolytically cleaves and inactivates factor Va. Disruptions that impair this down-regulatory feedback can provoke excessive clot formation (thrombophilia), whereas absolute deficiencies in factor V result in abnormal systemic bleeding.
Current Scientific Evidence and Clinical Evaluation
Scientific research into rs3948464 is largely characterized by its appearance as an incidental benign variant in thrombophilia panels and large-scale genetic association screens curated in resources like [ClinVar](https://www.ncbi.nlm.nih.gov/clinvar/?term=rs3948464) and the [EBI-NHGRI GWAS Catalog](https://www.ebi.ac.uk/gwas/search?query=rs3948464). Pathogenicity in F5 is primarily driven by well-characterized changes such as the Factor V Leiden mutation (p.Arg534Gln, historically numbered Arg506Gln), which creates activated protein C resistance. In contrast, population studies and clinical curation repositories consistently categorize rs3948464 as benign or likely benign. Although researchers have assessed whether minor background haplotypes in F5 subtly modulate plasma factor V levels or venous thromboembolism risk, evidence demonstrating a clinically meaningful independent effect for rs3948464 remains strictly limited or non-existent.
Population Frequency and Ancestral Distribution
According to broad population reference databases like the Genome Aggregation Database (gnomAD), rs3948464 is a highly prevalent polymorphism worldwide. The minor allele frequency (MAF) consistently hovers between 0.30 and 0.45 across diverse continental groups, meaning that a substantial portion of the global population carries at least one copy of the alternative allele. Homozygous genotypes are routinely encountered in healthy control cohorts across European, African, Asian, and Admixed American ancestries. The high frequency and widespread geographic presence of this variant in healthy individuals provide robust epidemiological support for its non-pathogenic, benign classification in medical genetics.
Interpreting Results: What You Can and Cannot Do
Discovering an rs3948464 genotype on an direct-to-consumer genetic report or exploratory panel does not indicate thrombophilia or a bleeding diathesis. This variant does not predict venous thromboembolism, pulmonary embolism, or abnormal clotting cascades on its own. It is essential not to confuse rs3948464 with pathogenic F5 mutations like Factor V Leiden. Individuals should never initiate, alter, or discontinue anticoagulants or any prescription therapy based on an rs3948464 result. Any personal or familial concerns regarding blood clotting, pregnancy-related thrombosis risks, or anticoagulant dosing should be thoroughly discussed with a licensed physician, hematologist, or pharmacist using validated clinical diagnostic tests.
How common is this variant?
The rs3948464 polymorphism is common across worldwide ancestries, demonstrating a minor allele frequency typically between 0.30 and 0.45 in broad reference populations.
Frequently asked questions
Is rs3948464 the same thing as Factor V Leiden?
No, rs3948464 is completely distinct from Factor V Leiden. Factor V Leiden is a specific missense mutation (p.Arg534Gln or Arg506Gln) that increases the risk of blood clots, whereas rs3948464 is considered a benign background variant.
Does having the rs3948464 variant mean I have a blood clotting disorder?
No, carrying this variant does not mean you have a clotting disorder or thrombophilia. Population databases demonstrate that it is widespread among healthy individuals without causing clinical complications.
Why does rs3948464 show up on my genetic test?
Clinical and commercial assays frequently sequence or probe entire genes related to cardiovascular health and coagulation. When analyzing the F5 gene, tests routinely detect harmless variations like rs3948464 alongside medically actionable mutations.
Should I change my medications or anticoagulant doses based on rs3948464?
No, you should never modify medications or anticoagulants based on rs3948464 results. Medical decisions and medication management must always be directed by a qualified healthcare professional in conjunction with clinical diagnostic testing.
Sources & further reading
Educational information only, last refreshed 9/7/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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