Thrombophilia due to protein S deficiency, autosomal recessive: genes and variants
Thrombophilia due to protein S deficiency, autosomal recessive is linked to 1 analyzed protein (PROS1). 26 DNA variants are known to cause it; 163 more are uncertain, and 1 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: thrombophilia due to protein S deficiency, autosomal dominant
Genes linked to Thrombophilia due to protein S deficiency, autosomal recessive
PROS1: Vitamin K-dependent protein S
It serves as an essential cofactor for activated protein C and also participates in TAM-receptor signaling involved in clearance of apoptotic cells. Heterozygous deficiency increases susceptibility to venous thrombosis, while severe deficiency can cause neonatal purpura fulminans.
26 disease-causing and 163 uncertain variants in PROS1 are linked to Thrombophilia due to protein S deficiency, autosomal recessive.
Where Thrombophilia due to protein S deficiency, autosomal recessive variants cluster
- PROS1 EGF-like 4 (positions 243–283): 4 of 26 disease-causing changes, 2.5× more than its size predicts.
- PROS1 EGF-like 2 (positions 157–200): 3 of 26 disease-causing changes, 1.8× more than its size predicts.
Known disease-causing variants in Thrombophilia due to protein S deficiency, autosomal recessive
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| PROS1 R355C | 355 | Laminin G-like 1 | Disease-causing (★★) |
| PROS1 C228W | 228 | EGF-like 3 | Disease-causing (★★) |
| PROS1 R355H | 355 | Laminin G-like 1 | Disease-causing (★★) |
| PROS1 P667L | 667 | Disease-causing (★★) | |
| PROS1 C639Y | 639 | Laminin G-like 2 | Disease-causing (★★) |
| PROS1 C186Y | 186 | EGF-like 2 | Disease-causing (★★) |
| PROS1 K196E | 196 | EGF-like 2 | Disease-causing (★★) |
| PROS1 R561W | 561 | Laminin G-like 2 | Disease-causing (★★) |
| PROS1 M1L | 1 | Disease-causing (★) | |
| PROS1 M1V | 1 | Disease-causing (★) | |
| PROS1 G52R | 52 | Gla | Disease-causing (★) |
| PROS1 C199R | 199 | EGF-like 2 | Disease-causing (★) |
| PROS1 C247S | 247 | EGF-like 4 | Disease-causing (★) |
| PROS1 C256S | 256 | EGF-like 4 | Disease-causing (★) |
| PROS1 Q362R | 362 | Laminin G-like 1 | Disease-causing (★) |
| PROS1 L446P | 446 | Laminin G-like 1 | Disease-causing (★) |
| PROS1 C475F | 475 | Laminin G-like 1 | Disease-causing (★) |
| PROS1 G621V | 621 | Laminin G-like 2 | Disease-causing (★) |
| PROS1 M640T | 640 | Laminin G-like 2 | Disease-causing (★) |
| PROS1 I562L | 562 | Laminin G-like 2 | Disease-causing (★) |
| PROS1 D278Y | 278 | EGF-like 4 | Disease-causing (★) |
| PROS1 N418Y | 418 | Laminin G-like 1 | Disease-causing (★) |
| PROS1 R515P | 515 | Laminin G-like 2 | Disease-causing (★) |
| PROS1 N258S | 258 | EGF-like 4 | Disease-causing |
| PROS1 G487R | 487 | Laminin G-like 2 | Disease-causing |
| PROS1 F635S | 635 | Laminin G-like 2 | Disease-causing |
Uncertain variants in Thrombophilia due to protein S deficiency, autosomal recessive that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| PROS1 C639F | 639 | Laminin G-like 2 | Uncertain (★) | +6: 2 other pathogenic changes within 3 positions; C639Y at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 0.97 |
Same protein, different disease
- Protein S deficiency disease is also caused by PROS1 variants; they fall mostly in different places as the Thrombophilia due to protein S deficiency, autosomal recessive variants (7 disease-causing).
Diseases related to Thrombophilia due to protein S deficiency, autosomal recessive
- Protein S deficiency disease, also linked to PROS1
Frequently asked questions
Which genes are linked to Thrombophilia due to protein S deficiency, autosomal recessive?
In CATVariant, Thrombophilia due to protein S deficiency, autosomal recessive is linked to 1 analyzed protein: PROS1 (Vitamin K-dependent protein S).
How many genetic variants are linked to Thrombophilia due to protein S deficiency, autosomal recessive?
213 variants: 26 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 163 are of uncertain significance or have conflicting reports.
Which uncertain variants in Thrombophilia due to protein S deficiency, autosomal recessive look disease-causing?
1 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example PROS1 C639F. These are leads for expert review, not diagnoses.
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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