Prothrombin deficiency: genes and variants
Prothrombin deficiency is linked to 1 analyzed protein (F2). 17 DNA variants are known to cause it; 41 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: congenital prothrombin deficiency
Genes linked to Prothrombin deficiency
F2: Prothrombin
After cleavage to thrombin, it converts fibrinogen to fibrin and activates multiple additional coagulation components to amplify clot formation. Deficiency can cause bleeding, whereas the common G20210A variant raises prothrombin levels and increases venous-thrombosis risk.
17 disease-causing and 41 uncertain variants in F2 are linked to Prothrombin deficiency.
Where Prothrombin deficiency variants cluster
- F2 Peptidase S1 (positions 364–618): 13 of 17 disease-causing changes, 1.9× more than its size predicts.
Known disease-causing variants in Prothrombin deficiency
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| F2 R596Q | 596 | Peptidase S1 | Disease-causing (★★) |
| F2 R461W | 461 | Peptidase S1 | Disease-causing (★★) |
| F2 R500Q | 500 | Peptidase S1 | Disease-causing (★★) |
| F2 R581C | 581 | Peptidase S1 | Disease-causing (★★) |
| F2 R425C | 425 | Peptidase S1 | Disease-causing (★) |
| F2 R596W | 596 | Peptidase S1 | Disease-causing (★) |
| F2 V424M | 424 | Peptidase S1 | Disease-causing (★) |
| F2 G499E | 499 | Peptidase S1 | Disease-causing (★) |
| F2 G332A | 332 | Disease-causing (★) | |
| F2 E357G | 357 | Disease-causing (★) | |
| F2 R425H | 425 | Peptidase S1 | Disease-causing |
| F2 D595E | 595 | Peptidase S1 | Disease-causing |
| F2 E352K | 352 | Disease-causing | |
| F2 E343K | 343 | Disease-causing | |
| F2 V365E | 365 | Peptidase S1 | Disease-causing |
| F2 M380T | 380 | Peptidase S1 | Disease-causing |
| F2 G601V | 601 | Peptidase S1 | Disease-causing |
Diseases related to Prothrombin deficiency
- Thrombophilia due to thrombin defect, also linked to F2
- Hereditary thrombophilia due to congenital protein C deficiency, also linked to F2
- Ischemic stroke, also linked to F2
- Pregnancy loss, recurrent, susceptibility to, 1, also linked to F2
Frequently asked questions
Which genes are linked to Prothrombin deficiency?
In CATVariant, Prothrombin deficiency is linked to 1 analyzed protein: F2 (Prothrombin).
How many genetic variants are linked to Prothrombin deficiency?
75 variants: 17 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 41 are of uncertain significance or have conflicting reports.
Which uncertain variants in Prothrombin deficiency look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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