PROS1 (Vitamin K-dependent protein S) variants and mutations
PROS1 (also known as Vitamin K-dependent protein S) is a human protein-coding gene encoding a vitamin K-dependent protein S protein. 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. This analysis covers 1,168 PROS1 variants and mutations. Of these, 71% have computational variant effect predictions. Disease context includes thrombophilia due to protein S deficiency, autosomal dominant, hereditary thrombophilia due to congenital protein S deficiency, and protein S deficiency. Example PROS1 variants include M1?, M1L, and M1V.
Variant analysis overview
- Gene: PROS1
- Protein: Vitamin K-dependent protein S
- UniProt accession: P07225
- Organism: Homo sapiens
- Variants analyzed: 1168
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 957 unspecified-consequence records; 4 splice-region variants; 100 missense variants; 95 synonymous variants; 6 frameshift variants; 4 stop-gained variants; 2 stop lost
- Prediction scores: 828 variants have prediction scores (71% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: thrombophilia due to protein S deficiency, autosomal dominant, hereditary thrombophilia due to congenital protein S deficiency, protein S deficiency, thrombophilia due to protein S deficiency, autosomal recessive, venous thromboembolism, pulmonary embolism, deep vein thrombosis, Thromboembolism, heart disorder, dengue disease, Pulmonary Infarction, blood coagulation disease.
Protein structure and variant hotspots
- Protein features: 7 domains; 15 post-translational modification sites.
- Structural context: 986 variants have structural context.
- PTM context: 20 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable PROS1 variants
Examples include M1?, M1L, M1V, R2K, R2S, L4M, L4V, G5S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, rs1403076049, ClinGen CA353674385, NCI-TCGA Cosmic COSV6239, ClinVar RCV002035461, MetaLR 0.86, MetaSVM 0.87, Pathogenic
- M1L (p.Met1Leu), rs2107279275, ClinGen CA353674391, ClinVar RCV001377708, MetaLR 0.77, MetaSVM 0.62, Likely pathogenic, not provided
- M1V (p.Met1Val), rs2107279275, ClinGen CA353674392, ClinVar RCV003528502, MetaLR 0.77, MetaSVM 0.62, Pathogenic, Thrombophilia due to protein S deficiency, autosomal recessive
- R2K (p.Arg2Lys), ExAC rs766252664, gnomAD rs766252664, REVEL 0.62, CADD 22.50, Uncertain significance, Thrombophilia due to protein S deficiency, autosomal recessive
- R2S (p.Arg2Ser), 1000Genomes rs566125037, ExAC rs566125037, TOPMed rs566125037, gnomAD rs566125037, REVEL 0.64, CADD 23.10, Uncertain significance, not provided
- L4M (p.Leu4Met), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L4V (p.Leu4Val), TOPMed rs1709927380
- G5S (p.Gly5Ser), ExAC rs763043055, gnomAD rs763043055, REVEL 0.14, CADD 5.35
- G6R (p.Gly6Arg), ExAC rs775508221, gnomAD rs775508221, REVEL 0.19, CADD 13.90
- R7L (p.Arg7Leu), rs1453399787, ClinGen CA353674351, ClinVar RCV003256833, TOPMed rs1453399787, REVEL 0.45, CADD 13.20, Uncertain significance, Inborn genetic diseases
- R7S (p.Arg7Ser), gnomAD rs1219702552, REVEL 0.22, CADD 14.30
- C8W (p.Cys8Trp), rs2471855615, ClinGen CA353674339, ClinVar RCV003037078, Uncertain significance, not provided
- G9R (p.Gly9Arg), gnomAD rs1189852497, NCI-TCGA Cosmic COSV1007, REVEL 0.12, CADD 7.40, Variant assessed as somatic; moderate impact.
- A10E (p.Ala10Glu), ExAC rs769834423, TOPMed rs769834423, gnomAD rs769834423, REVEL 0.41, CADD 17.20
- A10T (p.Ala10Thr), NCI-TCGA TCGA novel, Ensembl rs1709926755, Variant assessed as somatic; moderate impact.
- A10V (p.Ala10Val), ExAC rs769834423, TOPMed rs769834423, gnomAD rs769834423, REVEL 0.29, CADD 18.00
- L12P (p.Leu12Pro), TOPMed rs1347697005, Uncertain significance, Thrombophilia due to protein S deficiency, autosomal recessive
- L12Q (p.Leu12Gln), rs1347697005, ClinGen CA353674302, ClinVar RCV002044036, TOPMed rs1347697005, AlphaMissense 0.23, MetaLR 0.90, Uncertain significance, Thrombophilia due to protein S deficiency, autosomal recessive
- L12V (p.Leu12Val), ExAC rs781259302, gnomAD rs781259302, REVEL 0.61, CADD 22.50
- A13G (p.Ala13Gly), Ensembl rs2107279160
- C14Y (p.Cys14Tyr), ExAC rs771394908, gnomAD rs771394908, REVEL 0.41, CADD 17.00
- L15H (p.Leu15His), UniProt VAR 046802, Pathogenic, in THPH5
- L16F (p.Leu16Phe), gnomAD rs1323575023, REVEL 0.29, CADD 7.62
- L16P (p.Leu16Pro), rs1709925832, ClinGen CA353674245, ClinVar RCV001040853, Ensembl rs1709925832, AlphaMissense 0.18, MetaLR 0.73, Uncertain significance, Thrombophilia due to protein S deficiency, autosomal recessive
- V18A (p.Val18Ala), TOPMed rs1162049144, gnomAD rs1162049144, REVEL 0.19, CADD 13.00
- V18E (p.Val18Glu), UniProt VAR 046803, Pathogenic, in THPH5
- V18G (p.Val18Gly), TOPMed rs1162049144, gnomAD rs1162049144, REVEL 0.43, CADD 14.90
- V18L (p.Val18Leu), gnomAD rs1387038472, REVEL 0.11, CADD 8.81
- L19F (p.Leu19Phe), rs2471855514, ClinGen CA353674213, ClinVar RCV002905077, Uncertain significance, Inborn genetic diseases
- L19R (p.Leu19Arg), ExAC rs752290481, gnomAD rs752290481, REVEL 0.58, CADD 22.70, Uncertain significance, not provided
- P20H (p.Pro20His), TOPMed rs1709918238, gnomAD rs1709918238, REVEL 0.44, AlphaMissense 0.16
- P20R (p.Pro20Arg), rs1709918238, ClinGen CA353674207, ClinVar RCV002294842, AlphaMissense 0.16, MetaLR 0.83, Uncertain significance, Thrombophilia due to protein S deficiency, autosomal recessive
- P20S (p.Pro20Ser), TOPMed rs1709918301
- V21I (p.Val21Ile), rs754518511, ClinGen CA2503624, ClinVar RCV003175421, ExAC rs754518511, REVEL 0.23, CADD 9.12, Uncertain significance, Inborn genetic diseases
- V21L (p.Val21Leu), ExAC rs754518511, TOPMed rs754518511, gnomAD rs754518511, REVEL 0.23, CADD 9.14, Uncertain significance, Inborn genetic diseases
- F26I (p.Phe26Ile), ExAC rs753590699, gnomAD rs753590699
- F26V (p.Phe26Val), ExAC rs753590699, gnomAD rs753590699, REVEL 0.52, CADD 23.10
- L27=, NCI-TCGA Cosmic COSV1008, Variant assessed as somatic; low impact.
- L27F (p.Leu27Phe), 1000Genomes rs200631087, REVEL 0.48, CADD 20.00
- S28* (p.Ser28Ter), rs1576198449, ClinGen CA353674735, ClinVar RCV001027527, Ensembl rs1576198449, Pathogenic
- S28P (p.Ser28Pro), rs776526548, ClinGen CA2503594, ClinVar RCV002645488, ExAC rs776526548, REVEL 0.63, CADD 23.10, Uncertain significance, Inborn genetic diseases
- A32T (p.Ala32Thr), 1000Genomes rs192961830, ExAC rs192961830, gnomAD rs192961830, REVEL 0.82, CADD 26.00
- S33L (p.Ser33Leu), NCI-TCGA Cosmic COSV6239, REVEL 0.69, CADD 27.50, Variant assessed as somatic; moderate impact.
- V35A (p.Val35Ala), ExAC rs760850517, gnomAD rs760850517, REVEL 0.51, CADD 23.50
- V35F (p.Val35Phe), TOPMed rs1709035631
- V35I (p.Val35Ile), TOPMed rs1709035631
- V37D (p.Val37Asp), Ensembl rs1305704219
- V37F (p.Val37Phe), rs773551347, ClinGen CA353674679, ClinVar RCV002915074, ClinVar RCV003643036, REVEL 0.22, CADD 0.68, Uncertain significance, Inborn genetic diseases; Thrombophilia due to protein S deficiency, autosomal re
- V37L (p.Val37Leu), ExAC rs773551347, TOPMed rs773551347, gnomAD rs773551347, REVEL 0.17, CADD 0.36, Uncertain significance
- R38G (p.Arg38Gly), TOPMed rs1228905986
- R38S (p.Arg38Ser), Ensembl rs1576198423
- R38T (p.Arg38Thr), gnomAD rs1263100178, REVEL 0.79, CADD 24.50
- K39N (p.Lys39Asn), Ensembl rs2107203004
- R40C (p.Arg40Cys), rs772628286, ClinGen CA2503590, ClinVar RCV003642858, ExAC rs772628286, REVEL 0.84, CADD 26.70, Uncertain significance, Thrombophilia due to protein S deficiency, autosomal recessive
- R40H (p.Arg40His), rs7614835, ClinGen CA2503589, ClinVar RCV001299079, ClinVar RCV002493575, REVEL 0.77, CADD 25.20, Uncertain significance, Thrombophilia due to protein S deficiency, autosomal dominant; Thrombophilia due
- R40L (p.Arg40Leu), rs7614835, ClinGen CA2503588, ClinVar RCV000358997, ClinVar RCV000554713, REVEL 0.68, CADD 25.10, Conflicting interpretations, not specified; Thrombophilia due to protein S deficiency, autosomal recessive; P
- R41C (p.Arg41Cys), rs768994686, ClinGen CA2503587, ClinVar RCV003480121, ClinVar RCV005100299, REVEL 0.86, CADD 26.70, Conflicting interpretations, Thrombophilia due to protein S deficiency, autosomal recessive; not provided
- R41H (p.Arg41His), rs963668412, ClinGen CA78505726, NCI-TCGA Cosmic COSV6239, ClinVar RCV003484580, REVEL 0.93, CADD 26.00, Conflicting interpretations, Thrombophilia due to protein S deficiency, autosomal recessive; Thrombophilia du
- R41P (p.Arg41Pro), NCI-TCGA Cosmic COSV6239, REVEL 0.89, CADD 26.10, Variant assessed as somatic; moderate impact., in THPH5
- A42T (p.Ala42Thr), Ensembl rs865986114
- N43S (p.Asn43Ser), rs748858986, ClinGen CA2503586, ClinVar RCV000852006, ClinVar RCV003768319, REVEL 0.72, CADD 23.40, Uncertain significance, Thromboembolism; Thrombophilia due to protein S deficiency, autosomal recessive
- S44Y (p.Ser44Tyr), rs2471793910, ClinGen CA353674638, ClinVar RCV002777600, Uncertain significance, Inborn genetic diseases
- L46P (p.Leu46Pro), rs779469907, ClinGen CA2503584, ClinVar RCV000851694, ClinVar RCV005001996, REVEL 0.70, CADD 25.30, Conflicting interpretations, Thrombophilia due to protein S deficiency, autosomal dominant; Protein S deficie
- E47* (p.Glu47Ter), rs1709034856, ClinGen CA353674621, ClinVar RCV002245349, Ensembl rs1709034856, AlphaMissense 0.41, MetaLR 0.99, Pathogenic
- E47Q (p.Glu47Gln), rs1709034856, ClinGen CA353674622, NCI-TCGA Cosmic COSV1008, ClinVar RCV001266167, AlphaMissense 0.41, MetaLR 0.99, Uncertain significance, Inborn genetic diseases
- T49I (p.Thr49Ile), rs1386488557, gnomAD rs1386488557, REVEL 0.41, CADD 19.30, Variant assessed as somatic; moderate impact.
- T49S (p.Thr49Ser), gnomAD rs1386488557, REVEL 0.29, CADD 11.00
- K50E (p.Lys50Glu), rs748630360, ClinGen CA2503583, ClinVar RCV000851696, ClinVar RCV001320343, REVEL 0.83, CADD 24.90, Uncertain significance, Thrombophilia due to protein S deficiency, autosomal recessive; Thrombophilia du
- K50T (p.Lys50Thr), rs745579260, ClinGen CA2503582, ClinVar RCV000461718, ClinVar RCV004796187, REVEL 0.74, CADD 24.00, Uncertain significance, Thrombophilia due to protein S deficiency, autosomal dominant; Thrombophilia due
- Q51H (p.Gln51His), NCI-TCGA Cosmic COSV6239, Variant assessed as somatic; moderate impact.
- G52D (p.Gly52Asp), Ensembl rs1709034447, UniProt VAR 046807, Pathogenic, in THPH5
- G52R (p.Gly52Arg), rs2107202922, ClinGen CA353674586, ClinVar RCV001801308, Ensembl rs2107202922, AlphaMissense 0.84, MetaLR 1.00, Likely pathogenic, Thrombophilia due to protein S deficiency, autosomal dominant
- L54F (p.Leu54Phe), Ensembl rs2107202916
- L54P (p.Leu54Pro), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E55* (p.Glu55Ter), NCI-TCGA Cosmic COSV1008, Variant assessed as somatic; high impact.
- E55D (p.Glu55Asp), NCI-TCGA Cosmic COSV6239, REVEL 0.90, CADD 23.80, Variant assessed as somatic; moderate impact.
- R56G (p.Arg56Gly), ESP rs377491237, ExAC rs377491237, TOPMed rs377491237, gnomAD rs377491237, REVEL 0.92, CADD 24.90
- R56K (p.Arg56Lys), Ensembl rs764911524
- E57* (p.Glu57Ter), NCI-TCGA Cosmic COSV1008, Variant assessed as somatic; high impact.
- E57Q (p.Glu57Gln), ExAC rs757051970, gnomAD rs757051970, REVEL 0.90, CADD 25.80
- E57V (p.Glu57Val), ExAC rs751299946, gnomAD rs751299946, REVEL 0.97, CADD 29.40
- C58G (p.Cys58Gly), NCI-TCGA Cosmic COSV6239, Variant assessed as somatic; moderate impact.
- I59F (p.Ile59Phe), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- I59V (p.Ile59Val), Ensembl rs1709033990, REVEL 0.46, CADD 21.90
- E60K (p.Glu60Lys), rs758232970, NCI-TCGA Cosmic COSV6239, ExAC rs758232970, TOPMed rs758232970, REVEL 0.94, CADD 27.70, Uncertain significance, Thrombophilia due to protein S deficiency, autosomal recessive
- E61* (p.Glu61Ter), rs2107202868, ClinGen CA353674524, NCI-TCGA Cosmic COSV6239, Pathogenic
- E61K (p.Glu61Lys), NCI-TCGA Cosmic COSV6239, Uncertain significance, Thrombophilia due to protein S deficiency, autosomal dominant
- C63F (p.Cys63Phe), TOPMed rs1008457661, gnomAD rs1008457661
- N64S (p.Asn64Ser), gnomAD rs1192386862, REVEL 0.53, CADD 22.20
- K65E (p.Lys65Glu), NCI-TCGA Cosmic COSV6239, REVEL 0.81, CADD 27.40, Variant assessed as somatic; moderate impact.
- E67A (p.Glu67Ala), rs766423432, ClinGen CA2503575, ClinVar RCV001216716, ClinVar RCV002222676, REVEL 0.96, CADD 27.80, Conflicting interpretations, Thrombophilia due to protein S deficiency, autosomal dominant; Thrombophilia due
- E67K (p.Glu67Lys), rs2471793830, ClinGen CA353674482, ClinVar RCV003480116, Likely pathogenic, not provided
- A68D (p.Ala68Asp), UniProt VAR 046809, Pathogenic, in THPH5
- A68G (p.Ala68Gly), TOPMed rs1268026904, gnomAD rs1268026904
- A68V (p.Ala68Val), TOPMed rs1268026904, gnomAD rs1268026904, REVEL 0.87, CADD 27.30, Uncertain significance, Inborn genetic diseases
- R69T (p.Arg69Thr), gnomAD rs1709033270, REVEL 0.93, CADD 25.50
- V71F (p.Val71Phe), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- F72C (p.Phe72Cys), UniProt VAR 046810, Pathogenic, in THPH5
- F72S (p.Phe72Ser), rs2471793821, ClinGen CA353674445, ClinVar RCV003594626, Likely pathogenic, Protein S deficiency disease
- N74D (p.Asn74Asp), TOPMed rs1709033084, REVEL 0.72, CADD 27.40
- N74I (p.Asn74Ile), NCI-TCGA Cosmic COSV6239, Variant assessed as somatic; moderate impact.
- D75E (p.Asp75Glu), NCI-TCGA Cosmic COSV1008, Variant assessed as somatic; moderate impact.
- D75V (p.Asp75Val), TOPMed rs1433602733, gnomAD rs1433602733, REVEL 0.34, CADD 22.90
- D75Y (p.Asp75Tyr), NCI-TCGA Cosmic COSV6239, REVEL 0.34, CADD 15.10, Variant assessed as somatic; moderate impact.
- P76L (p.Pro76Leu), rs73846070, ClinGen CA2503573, ClinVar RCV000650163, ClinVar RCV001084203, REVEL 0.67, CADD 23.50, Conflicting interpretations, not specified; not provided; Thrombophilia due to protein S deficiency, autosoma
- E77K (p.Glu77Lys), NCI-TCGA Cosmic COSV6239, Variant assessed as somatic; moderate impact.
- T78=, NCI-TCGA Cosmic COSV6240, Variant assessed as somatic; low impact., in THPH5
- T78M (p.Thr78Met), rs6122, ClinGen CA337558, ClinVar RCV000197958, ClinVar RCV000851741, REVEL 0.96, CADD 31.00, Conflicting interpretations, Thrombophilia due to protein S deficiency, autosomal dominant; Thrombophilia due
- D79A (p.Asp79Ala), ExAC rs770400563, TOPMed rs770400563, gnomAD rs770400563
- D79G (p.Asp79Gly), ExAC rs770400563, TOPMed rs770400563, gnomAD rs770400563, REVEL 0.59, CADD 24.80
- D79V (p.Asp79Val), ExAC rs770400563, TOPMed rs770400563, gnomAD rs770400563, REVEL 0.62, CADD 25.70, Uncertain significance, Thrombophilia due to protein S deficiency, autosomal recessive
- D79Y (p.Asp79Tyr), rs776082764, ClinGen CA2503547, ClinVar RCV003529475, ExAC rs776082764, REVEL 0.81, CADD 35.00, Uncertain significance, Thrombophilia due to protein S deficiency, autosomal recessive
- Y80H (p.Tyr80His), ESP rs145704559, ExAC rs145704559, TOPMed rs145704559, gnomAD rs145704559, REVEL 0.84, CADD 26.80
- Y82D (p.Tyr82Asp), gnomAD rs1708985265, REVEL 0.95, CADD 27.40
- P83R (p.Pro83Arg), NCI-TCGA TCGA novel, REVEL 0.84, CADD 26.30, Variant assessed as somatic; moderate impact.
- P83S (p.Pro83Ser), gnomAD rs1247384316, REVEL 0.76, CADD 28.40
- K84E (p.Lys84Glu), TOPMed rs1187533518, gnomAD rs1187533518, REVEL 0.82, CADD 24.90
- Y85D (p.Tyr85Asp), rs2471789475, ClinGen CA353674256, ClinVar RCV003810713, Uncertain significance, Thrombophilia due to protein S deficiency, autosomal recessive
- V87F (p.Val87Phe), NCI-TCGA Cosmic COSV6239, REVEL 0.49, CADD 34.00, Variant assessed as somatic; moderate impact., in THPH5
- V87I (p.Val87Ile), NCI-TCGA Cosmic COSV6239, Variant assessed as somatic; moderate impact., in THPH5
- V87L (p.Val87Leu), rs557733421, UniProt VAR 046812, 1000Genomes rs557733421, ExAC rs557733421, REVEL 0.44, CADD 32.00, Pathogenic, in THPH5
- C88Y (p.Cys88Tyr), rs2472148966, ClinGen CA353674152, ClinVar RCV003484581, UniProt VAR 046813, Conflicting interpretations, Thrombophilia due to protein S deficiency, autosomal dominant
- L89F (p.Leu89Phe), rs1708748113, ClinGen CA353674145, ClinVar RCV003088766, TOPMed rs1708748113, REVEL 0.72, CADD 24.70, Uncertain significance, Thrombophilia due to protein S deficiency, autosomal recessive
- L89P (p.Leu89Pro), rs1708748069, ClinGen CA353674143, ClinVar RCV003821468, Ensembl rs1708748069, AlphaMissense 0.91, MetaLR 0.99, Uncertain significance, Thrombophilia due to protein S deficiency, autosomal recessive
- R90C (p.Arg90Cys), rs765935815, ClinGen CA2503527, NCI-TCGA Cosmic COSV6239, ClinVar RCV003529474, REVEL 0.68, CADD 23.10, Uncertain significance, Thrombophilia due to protein S deficiency, autosomal dominant; Thrombophilia due
- R90H (p.Arg90His), rs200886866, ClinGen CA2503526, ClinVar RCV001213586, UniProt VAR 046815, REVEL 0.64, CADD 21.50, Uncertain significance, Thrombophilia due to protein S deficiency, autosomal recessive
- R90P (p.Arg90Pro), rs200886866, ClinGen CA353674139, ClinVar RCV001205963, ExAC rs200886866, REVEL 0.62, CADD 23.20, Uncertain significance, Thrombophilia due to protein S deficiency, autosomal recessive
- S91C (p.Ser91Cys), gnomAD rs1411206237, REVEL 0.62, AlphaMissense 0.12
- S91Y (p.Ser91Tyr), rs1411206237, NCI-TCGA Cosmic COSV6239, gnomAD rs1411206237, AlphaMissense 0.12, MetaLR 0.97, Variant assessed as somatic; moderate impact.
- F92C (p.Phe92Cys), ExAC rs772748769, gnomAD rs772748769, REVEL 0.66, CADD 24.20
- Q93* (p.Gln93Ter), TOPMed rs1708747715
- T94A (p.Thr94Ala), 1000Genomes rs200093789
- T94I (p.Thr94Ile), TOPMed rs1377930462, gnomAD rs1377930462, REVEL 0.32, CADD 7.84
- G95E (p.Gly95Glu), rs144526169, ClinGen CA211753, ClinVar RCV000148760, ClinVar RCV000851762, REVEL 0.72, CADD 20.80, Conflicting interpretations, not provided; Thrombophilia due to protein S deficiency, autosomal dominant; Thr
- G95R (p.Gly95Arg), UniProt VAR 046817, Pathogenic, in THPH5
- G95W (p.Gly95Trp), NCI-TCGA Cosmic COSV1008, Variant assessed as somatic; moderate impact., in THPH5
- L96F (p.Leu96Phe), Ensembl rs2107177900
- F97S (p.Phe97Ser), Ensembl rs1708747500
- T98A (p.Thr98Ala), ExAC rs747923334, TOPMed rs747923334, gnomAD rs747923334, REVEL 0.10, CADD 5.21
- T98I (p.Thr98Ile), 1000Genomes rs142805170, ESP rs142805170, ExAC rs142805170, TOPMed rs142805170, REVEL 0.15, CADD 5.39, Uncertain significance
- T98S (p.Thr98Ser), rs142805170, ClinGen CA2503523, ClinVar RCV002245346, ClinVar RCV002502056, REVEL 0.07, CADD 0.46, Uncertain significance, Thrombophilia due to protein S deficiency, autosomal recessive; Thrombophilia du
- A99G (p.Ala99Gly), Ensembl rs1708747258, REVEL 0.16, CADD 16.40
- A99S (p.Ala99Ser), Ensembl rs2107177885
- A99V (p.Ala99Val), NCI-TCGA Cosmic COSV1008, REVEL 0.23, CADD 16.60, Variant assessed as somatic; moderate impact.
- A100E (p.Ala100Glu), ESP rs375363379, ExAC rs375363379, TOPMed rs375363379, gnomAD rs375363379, REVEL 0.17, CADD 9.83
- A100S (p.Ala100Ser), gnomAD rs1457029951, REVEL 0.13, CADD 11.50
- A100V (p.Ala100Val), NCI-TCGA Cosmic COSV6239, Uncertain significance, Inborn genetic diseases
- R101C (p.Arg101Cys), rs778731080, ClinGen CA78494166, ClinVar RCV003110564, ClinVar RCV003994523, REVEL 0.63, CADD 24.80, Conflicting interpretations, Thrombophilia due to protein S deficiency, autosomal dominant; Thrombophilia due
- R101H (p.Arg101His), TOPMed rs1470600953, gnomAD rs1470600953, REVEL 0.31, CADD 22.60
- R101L (p.Arg101Leu), TOPMed rs1470600953, gnomAD rs1470600953, REVEL 0.33, CADD 22.30
- Q102L (p.Gln102Leu), TOPMed rs1708746509
- S103L (p.Ser103Leu), NCI-TCGA Cosmic COSV6239, Variant assessed as somatic; moderate impact.
- T104A (p.Thr104Ala), Ensembl rs754897308, REVEL 0.15, CADD 6.63
- T104N (p.Thr104Asn), rs753950548, ClinGen CA78494154, ClinVar RCV001144368, TOPMed rs753950548, REVEL 0.30, CADD 15.10, Uncertain significance, Thrombophilia due to protein S deficiency, autosomal dominant
- N105S (p.Asn105Ser), rs372589167, ESP rs372589167, TOPMed rs372589167, gnomAD rs372589167, REVEL 0.19, CADD 13.20, Variant assessed as somatic; moderate impact.
- A106T (p.Ala106Thr), Ensembl rs1576189631
- Y107I (p.Tyr107Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- P108S (p.Pro108Ser), TOPMed rs1708746199, Uncertain significance, Inborn genetic diseases
- P108T (p.Pro108Thr), NCI-TCGA TCGA novel, TOPMed rs1708746199, REVEL 0.15, CADD 9.42, Uncertain significance, Thrombophilia due to protein S deficiency, autosomal recessive
- L110I (p.Leu110Ile), NCI-TCGA Cosmic COSV6239, REVEL 0.57, CADD 24.00, Variant assessed as somatic; moderate impact.
- L110R (p.Leu110Arg), Ensembl rs1708746146, REVEL 0.82, CADD 28.10
- R111S (p.Arg111Ser), UniProt VAR 046820, Pathogenic, in THPH5
- S112I (p.Ser112Ile), NCI-TCGA Cosmic COSV6239, Variant assessed as somatic; moderate impact.
- S112N (p.Ser112Asn), gnomAD rs1708745951, REVEL 0.34, CADD 23.00
- C113F (p.Cys113Phe), ExAC rs757418321, gnomAD rs757418321, REVEL 0.91, CADD 26.60, Uncertain significance, not provided; Thrombophilia due to protein S deficiency, autosomal recessive
- V114I (p.Val114Ile), TOPMed rs1708745826
- N115S (p.Asn115Ser), TOPMed rs1021844343, gnomAD rs1021844343, REVEL 0.17, CADD 12.10
- P118L (p.Pro118Leu), rs761574063, ClinGen CA2503502, ClinVar RCV000851642, ExAC rs761574063, REVEL 0.36, CADD 24.90, Likely pathogenic, Protein S deficiency disease
- P118S (p.Pro118Ser), gnomAD rs1227056282, REVEL 0.20, CADD 16.90
- D119E (p.Asp119Glu), NCI-TCGA Cosmic COSV6239, Variant assessed as somatic; moderate impact.
- D119G (p.Asp119Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- Q120E (p.Gln120Glu), TOPMed rs1471724817, gnomAD rs1471724817, REVEL 0.69, CADD 25.40, Uncertain significance, Thrombophilia due to protein S deficiency, autosomal recessive
- Q120K (p.Gln120Lys), TOPMed rs1471724817, gnomAD rs1471724817, REVEL 0.71, CADD 26.30
- C121Y (p.Cys121Tyr), UniProt VAR 046821, Pathogenic, not provided
- S122C (p.Ser122Cys), ExAC rs774133229, gnomAD rs774133229, REVEL 0.36, CADD 22.20
- S122N (p.Ser122Asn), ExAC rs768639397, gnomAD rs768639397, REVEL 0.24, CADD 13.30
- P123A (p.Pro123Ala), gnomAD rs1258458602, REVEL 0.70, CADD 25.30
- P123L (p.Pro123Leu), gnomAD rs866561381, REVEL 0.76, CADD 27.10
- P123R (p.Pro123Arg), gnomAD rs866561381, REVEL 0.78, CADD 26.50
- P123S (p.Pro123Ser), gnomAD rs1258458602, REVEL 0.63, CADD 26.60
Public PROS1 analysis runs
- PROS1 analysis run — PROS1 (1,168 variants) — completed 2026-08-19