Von Willebrand disorder: genes and variants
Von Willebrand disorder is linked to 1 analyzed protein (VWF). 12 DNA variants are known to cause it; 3 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Von Willebrand disorder
VWF: von Willebrand factor
It tethers platelets to damaged vessel walls and carries factor VIII in the circulation, linking primary hemostasis with coagulation. Quantitative or qualitative pathogenic variants cause von Willebrand disease, the most common inherited bleeding disorder.
12 disease-causing and 3 uncertain variants in VWF are linked to Von Willebrand disorder.
Where Von Willebrand disorder variants cluster
- VWF VWFA 1 (positions 1277–1453): 5 of 12 disease-causing changes, 6.6× more than its size predicts.
Known disease-causing variants in Von Willebrand disorder
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| VWF A1437T | 1437 | VWFA 1 | Disease-causing (★★★★) |
| VWF I1416T | 1416 | VWFA 1 | Disease-causing (★★) |
| VWF I1416N | 1416 | VWFA 1 | Disease-causing (★★) |
| VWF T1156M | 1156 | TIL 4 | Disease-causing (★★) |
| VWF R1315C | 1315 | VWFA 1 | Disease-causing (★★) |
| VWF R1374C | 1374 | VWFA 1 | Disease-causing (★★) |
| VWF K1794E | 1794 | VWFA 3 | Disease-causing (★★) |
| VWF S2179F | 2179 | Disease-causing (★★) | |
| VWF R2464C | 2464 | VWFC 2 | Disease-causing (★★) |
| VWF R1205C | 1205 | Disease-causing (★★) | |
| VWF C2237R | 2237 | E2 | Disease-causing (★) |
| VWF R760H | 760 | Disease-causing (★) |
Which prediction tools work for Von Willebrand disorder
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- CATVariant: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- MetaLR: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 95 out of 100
- CADD: 94 out of 100
- REVEL: 94 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- PolyPhen-2: 91 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- phyloP: 88 out of 100
Same protein, different disease
- Von Willebrand disease is also caused by VWF variants; they fall mostly in different places as the Von Willebrand disorder variants (112 disease-causing).
- Hereditary von Willebrand disease is also caused by VWF variants; they fall mostly in different places as the Von Willebrand disorder variants (26 disease-causing).
Diseases related to Von Willebrand disorder
- Hypertrophic cardiomyopathy, also linked to VWF
- Noonan syndrome, also linked to VWF
- Von Willebrand disease, also linked to VWF
- Hereditary von Willebrand disease, also linked to VWF
- Thrombotic thrombocytopenic purpura, also linked to VWF
Frequently asked questions
Which genes are linked to Von Willebrand disorder?
In CATVariant, Von Willebrand disorder is linked to 1 analyzed protein: VWF (von Willebrand factor).
How many genetic variants are linked to Von Willebrand disorder?
15 variants: 12 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 3 are of uncertain significance or have conflicting reports.
Which uncertain variants in Von Willebrand disorder look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
Which variant effect predictor works best for Von Willebrand disorder?
Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.95, based on 12 disease-causing and 37 harmless variants).
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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