PMS1 (PMS1 protein homolog 1) variants and mutations
PMS1 (also known as PMS1 protein homolog 1) is a human protein-coding gene encoding a PMS1 protein homolog 1 protein. It participates in DNA mismatch repair through complexes with MLH-family proteins, although its role is less central than that of PMS2 in canonical MutLalpha activity. Germline variants have been investigated in cancer predisposition, but many reported associations remain less definitive than core Lynch-syndrome genes. This analysis covers 1,649 PMS1 variants and mutations. Of these, 66% have computational variant effect predictions. Disease context includes colorectal cancer, ovarian cancer, and Lynch syndrome. Example PMS1 variants include Q3P, Q3Q, and Q3H.
Variant analysis overview
- Gene: PMS1
- Protein: PMS1 protein homolog 1
- UniProt accession: P54277
- Organism: Homo sapiens
- Variants analyzed: 1649
- Variant scope: all variants
- Completed: 2026-08-22
Variant and mutation evidence
- Variant composition: 1,419 unspecified-consequence records; 67 synonymous variants; 113 missense variants; 37 frameshift variants; 6 stop-gained variants; 4 in-frame deletions; 2 splice-region variants; 1 splice acceptor variant; 1 in-frame insertions; 1 substitution
- Prediction scores: 1,090 variants have prediction scores (66% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: colorectal cancer, ovarian cancer, Lynch syndrome, Retinal dystrophy, hepatocellular carcinoma, lung carcinoma, breast carcinoma, thyroid gland carcinoma, oral cavity squamous cell carcinoma, melanoma, head and neck squamous cell carcinoma, squamous cell lung carcinoma.
Protein structure and variant hotspots
- Experimental data: 62 protein positions have experimental scores. Source: PMS1 High mobility group box domain domainome 1.0.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable PMS1 variants
Examples include Q3P, Q3Q, Q3H, L4S, L4M, L4L, P5H, P5S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- Q3P (p.Gln3Pro), Ensembl rs2106212459, REVEL 0.59, CADD 23.60
- Q3Q (p.Gln3Gln), rs373031044, gnomAD 2-189791818-A-G, CADD 9.98
- Q3H (p.Gln3His), gnomAD 2-189791818-A-C, REVEL 0.36, CADD 17.70
- L4S (p.Leu4Ser), 1000Genomes rs201944922, REVEL 0.89, CADD 28.40
- L4M (p.Leu4Met), gnomAD 2-189791819-T-A, REVEL 0.79, CADD 24.70
- L4L (p.Leu4Leu), gnomAD 2-189791819-T-C, CADD 12.80
- P5H (p.Pro5His), Ensembl rs866654894
- P5S (p.Pro5Ser), Ensembl rs2106212504, REVEL 0.29, CADD 16.20
- P5T (p.Pro5Thr), Ensembl rs2106212504
- P5R (p.Pro5Arg), gnomAD 2-189791823-C-G, REVEL 0.85, CADD 26.30
- P5P (p.Pro5Pro), rs778660303, gnomAD 2-189791824-T-C, CADD 13.80
- A6E (p.Ala6Glu), ExAC rs747835603, TOPMed rs747835603, gnomAD rs747835603
- A6G (p.Ala6Gly), ExAC rs747835603, TOPMed rs747835603, gnomAD rs747835603, REVEL 0.42, CADD 22.70
- A6V (p.Ala6Val), cosmic curated COSV59714, ExAC rs747835603, TOPMed rs747835603, gnomAD rs747835603, REVEL 0.45, CADD 23.90
- A6A (p.Ala6Ala), rs771930754, gnomAD 2-189791827-G-C, CADD 10.20
- A7T (p.Ala7Thr), Ensembl rs2106212584
- T8A (p.Thr8Ala), ExAC rs777641087, TOPMed rs777641087, gnomAD rs777641087, REVEL 0.78, CADD 26.10
- T8I (p.Thr8Ile), gnomAD rs1367989549, REVEL 0.83, CADD 26.30
- T8S (p.Thr8Ser), ExAC rs777641087, TOPMed rs777641087, gnomAD rs777641087
- T8R (p.Thr8Arg), gnomAD 2-189791832-C-G, REVEL 0.93, CADD 25.60
- V9I (p.Val9Ile), gnomAD 2-189791834-G-A, REVEL 0.23, CADD 16.60
- R10* (p.Arg10Ter), rs1367090018, cosmic curated COSV59721, TOPMed rs1367090018, CADD 36.00, Variant assessed as somatic; high impact.
- R10Q (p.Arg10Gln), cosmic curated COSV59715, 1000Genomes rs370084230, ESP rs370084230, ExAC rs370084230, REVEL 0.78, CADD 31.00
- R10D (p.Arg10Asp), gnomAD 2-189791836-TC-T, CADD 26.10
- R10L (p.Arg10Leu), gnomAD 2-189791838-G-T, REVEL 0.90, CADD 31.00
- R10R (p.Arg10Arg), gnomAD 2-189791839-A-G, CADD 11.10
- L11F (p.Leu11Phe), cosmic curated COSV59718, Ensembl rs2048895274
- L11P (p.Leu11Pro), ExAC rs770894099, TOPMed rs770894099, gnomAD rs770894099, REVEL 0.86, CADD 31.00
- L11R (p.Leu11Arg), ExAC rs770894099, TOPMed rs770894099, gnomAD rs770894099, REVEL 0.74, CADD 28.10, Uncertain significance, not specified
- L11I (p.Leu11Ile), gnomAD 2-189791840-C-A, REVEL 0.57, CADD 24.90
- L11L (p.Leu11Leu), rs762260830, gnomAD 2-189791842-C-T, CADD 9.91
- L12F (p.Leu12Phe), ESP rs374261058, ExAC rs374261058, TOPMed rs374261058, gnomAD rs374261058, REVEL 0.81, CADD 23.80
- L12I (p.Leu12Ile), ESP rs374261058, ExAC rs374261058, TOPMed rs374261058, gnomAD rs374261058, REVEL 0.55, CADD 22.40
- S13L (p.Ser13Leu), rs1377084219, NCI-TCGA Cosmic COSV1005, cosmic curated COSV10057, TOPMed rs1377084219, REVEL 0.84, CADD 28.00, Variant assessed as somatic; moderate impact.
- S13* (p.Ser13Ter), gnomAD 2-189791847-C-G, CADD 35.00
- S13S (p.Ser13Ser), rs2106212776, gnomAD 2-189791848-A-G, CADD 11.70
- S14G (p.Ser14Gly), ExAC rs775649361, TOPMed rs775649361, gnomAD rs775649361, REVEL 0.95, CADD 28.60
- S14N (p.Ser14Asn), ExAC rs763166242, gnomAD rs763166242, REVEL 0.86, CADD 28.30
- S15Y (p.Ser15Tyr), Ensembl rs2106212811
- S15F (p.Ser15Phe), gnomAD 2-189791853-C-T, REVEL 0.86, CADD 26.90
- S15S (p.Ser15Ser), rs377616727, gnomAD 2-189791854-T-A, CADD 12.50
- Q16* (p.Gln16Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- Q16R (p.Gln16Arg), 1000Genomes rs570876790, ExAC rs570876790, gnomAD rs570876790, REVEL 0.92, CADD 26.90
- Q16E (p.Gln16Glu), gnomAD 2-189791855-C-G, REVEL 0.62, CADD 24.90
- I17V (p.Ile17Val), ESP rs151231718, ExAC rs151231718, TOPMed rs151231718, gnomAD rs151231718, REVEL 0.28, CADD 15.90
- I18V (p.Ile18Val), Ensembl rs2106212892, REVEL 0.44, CADD 25.10
- T19A (p.Thr19Ala), Ensembl rs2048897350, REVEL 0.57, CADD 25.30
- T19S (p.Thr19Ser), 1000Genomes rs534847551, ExAC rs534847551, TOPMed rs534847551, gnomAD rs534847551, REVEL 0.52, CADD 23.50
- T19T (p.Thr19Thr), gnomAD 2-189791866-T-A, CADD 8.69
- S20L (p.Ser20Leu), cosmic curated COSV59718, ExAC rs768047966, TOPMed rs768047966, gnomAD rs768047966, REVEL 0.90, CADD 28.90
- S20S (p.Ser20Ser), rs750916185, gnomAD 2-189791869-G-A, CADD 5.80
- V21M (p.Val21Met), Ensembl rs2106212967, REVEL 0.75, CADD 28.20
- V21V (p.Val21Val), rs754498304, gnomAD 2-189791872-G-T, CADD 10.10
- V22I (p.Val22Ile), gnomAD rs1247011280, REVEL 0.51, CADD 23.00
- V22L (p.Val22Leu), NCI-TCGA Cosmic COSV1005, cosmic curated COSV10057, REVEL 0.41, CADD 22.10, Variant assessed as somatic; moderate impact.
- V22V (p.Val22Val), gnomAD 2-189791875-C-A, CADD 16.50
- S23G (p.Ser23Gly), gnomAD 2-189791876-A-G, REVEL 0.73, CADD 27.20
- S23N (p.Ser23Asn), gnomAD 2-189791877-G-A, REVEL 0.41, CADD 22.60
- V24A (p.Val24Ala), gnomAD rs1265410375
- V24I (p.Val24Ile), rs553130827, NCI-TCGA Cosmic COSV1005, cosmic curated COSV10057, 1000Genomes rs553130827, REVEL 0.72, CADD 27.00, Variant assessed as somatic; moderate impact.
- V25I (p.Val25Ile), TOPMed rs1224767088, REVEL 0.39, CADD 25.20
- V25L (p.Val25Leu), TOPMed rs1224767088, REVEL 0.70, CADD 25.70
- K26K (p.Lys26Lys), rs2048899529, gnomAD 2-189791887-A-G, CADD 13.60
- E27G (p.Glu27Gly), gnomAD rs1472063251, REVEL 0.93, CADD 32.00
- E27Q (p.Glu27Gln), rs5742973, ClinGen CA2026282, ClinVar RCV000735969, ClinVar RCV004692215, REVEL 0.82, CADD 28.70, Uncertain significance, Polyp of colon; not provided
- L28F (p.Leu28Phe), Ensembl rs2106213113, Uncertain significance, not specified
- I29F (p.Ile29Phe), gnomAD rs1162761263, REVEL 0.76, CADD 23.20
- I29T (p.Ile29Thr), gnomAD rs1198535898, REVEL 0.82, CADD 26.70
- I29V (p.Ile29Val), gnomAD 2-189791894-A-G, REVEL 0.33, CADD 12.80
- I29S (p.Ile29Ser), gnomAD 2-189791895-T-G, REVEL 0.90, CADD 31.00
- I29I (p.Ile29Ile), gnomAD 2-189791896-T-C, CADD 13.60
- N31H (p.Asn31His), gnomAD 2-189791900-A-C, REVEL 0.95, CADD 27.00
- N31T (p.Asn31Thr), gnomAD 2-189791901-A-C, REVEL 0.95, CADD 27.60
- N31N (p.Asn31Asn), rs1282042919, gnomAD 2-189791902-C-T, CADD 12.90
- S32C (p.Ser32Cys), gnomAD rs1481320634, REVEL 0.91, CADD 26.70
- S32T (p.Ser32Thr), gnomAD rs1256785630, REVEL 0.83, CADD 25.90
- S32P (p.Ser32Pro), gnomAD 2-189791903-T-C, REVEL 0.88, CADD 29.30
- S32F (p.Ser32Phe), gnomAD 2-189791904-C-T, REVEL 0.95, CADD 27.20
- S32S (p.Ser32Ser), gnomAD 2-189791905-C-A, CADD 12.00
- L33V (p.Leu33Val), TOPMed rs1385709157, gnomAD rs1385709157, REVEL 0.72, CADD 23.50
- L33W (p.Leu33Trp), gnomAD 2-189791905-CT-C, CADD 23.50
- L33L (p.Leu33Leu), rs1385709157, gnomAD 2-189791906-T-C, CADD 12.10
- D34V (p.Asp34Val), TOPMed rs2048902100
- D34W (p.Asp34Trp), rs1177278769, gnomAD 2-189791906-T-TTG, CADD 28.70
- D34N (p.Asp34Asn), gnomAD 2-189791909-G-A, REVEL 0.86, CADD 31.00
- A35D (p.Ala35Asp), Ensembl rs2106213260
- A35V (p.Ala35Val), cosmic curated COSV10057, Ensembl rs2106213260
- A35G (p.Ala35Gly), gnomAD 2-189791913-C-G, REVEL 0.89, CADD 25.40
- A35A (p.Ala35Ala), rs1318842000, gnomAD 2-189791914-T-C, CADD 7.18
- G36D (p.Gly36Asp), Ensembl rs2106213299, REVEL 0.68, CADD 23.70
- G36S (p.Gly36Ser), TOPMed rs781053212, gnomAD rs781053212, REVEL 0.51, CADD 22.70
- G36A (p.Gly36Ala), gnomAD 2-189791916-G-C, REVEL 0.69, CADD 23.60
- A37S (p.Ala37Ser), TOPMed rs973362695, gnomAD rs973362695, REVEL 0.68, CADD 26.50
- A37T (p.Ala37Thr), TOPMed rs973362695, gnomAD rs973362695
- A37V (p.Ala37Val), Ensembl rs2106213330, REVEL 0.89, CADD 27.20
- T38A (p.Thr38Ala), TOPMed rs2048902971, Uncertain significance, not specified
- p.Thr38 Val40delinsIle, rs761879899, gnomAD 2-189791921-ACAAG, CADD 21.70
- T38I (p.Thr38Ile), gnomAD 2-189791922-C-T, REVEL 0.84, CADD 26.00
- T38R (p.Thr38Arg), gnomAD 2-189791922-C-G, REVEL 0.72, CADD 25.50
- T38T (p.Thr38Thr), rs758112220, gnomAD 2-189791923-A-T, CADD 11.00
- S39G (p.Ser39Gly), ESP rs113193813, TOPMed rs113193813, gnomAD rs113193813, REVEL 0.65, CADD 24.40, Uncertain significance, not specified
- S39R (p.Ser39Arg), ExAC rs777358818, gnomAD rs777358818, REVEL 0.70, CADD 28.80
- S39T (p.Ser39Thr), TOPMed rs2048904085, gnomAD rs2048904085, REVEL 0.30, CADD 23.20
- S39S (p.Ser39Ser), rs777358818, gnomAD 2-189791926-C-T, CADD 13.70
- V40I (p.Val40Ile), ExAC rs746784366, gnomAD rs746784366, REVEL 0.23, CADD 14.70
- V40V (p.Val40Val), rs1352280321, gnomAD 2-189791929-A-G, CADD 11.60
- D41A (p.Asp41Ala), cosmic curated COSV10463, ExAC rs545600556, TOPMed rs545600556, gnomAD rs545600556, REVEL 0.83, CADD 29.20
- D41G (p.Asp41Gly), ExAC rs545600556, TOPMed rs545600556, gnomAD rs545600556, REVEL 0.87, CADD 31.00
- D41H (p.Asp41His), ExAC rs757048301, gnomAD rs757048301, REVEL 0.71, CADD 30.00
- V42D (p.Val42Asp), Ensembl rs2106213460
- V42I (p.Val42Ile), Ensembl rs2106213450
- V42V (p.Val42Val), rs769797470, gnomAD 2-189791935-T-G, CADD 9.19
- L44L (p.Leu44Leu), rs2048906405, gnomAD 2-189791939-C-T, CADD 16.70
- E45D (p.Glu45Asp), NCI-TCGA Cosmic COSV5971, cosmic curated COSV59715, Variant assessed as somatic; moderate impact.
- E45del (p.Glu45del), gnomAD 2-189795766-TAGG-, CADD 34.00
- N46K (p.Asn46Lys), Ensembl rs2106232835
- N46S (p.Asn46Ser), TOPMed rs1477413205, gnomAD rs1477413205, REVEL 0.69, CADD 23.70
- N46T (p.Asn46Thr), rs2049300713, gnomAD 2-189795770-AG-A, CADD 23.40
- Y47C (p.Tyr47Cys), cosmic curated COSV59716, ExAC rs756031414, gnomAD rs756031414, REVEL 0.50, CADD 22.60
- Y47H (p.Tyr47His), gnomAD 2-189795775-T-C, REVEL 0.32, CADD 23.50
- Y47Y (p.Tyr47Tyr), rs5742980, gnomAD 2-189795777-T-C, CADD 8.34
- G48E (p.Gly48Glu), TOPMed rs1180123369, gnomAD rs1180123369
- G48R (p.Gly48Arg), TOPMed rs2049301792, REVEL 0.86, CADD 32.00
- G48* (p.Gly48Ter), gnomAD 2-189795778-G-T, CADD 40.00
- F49W (p.Phe49Trp), rs1168435979, gnomAD 2-189795775-T-TAT, CADD 27.10
- D50H (p.Asp50His), gnomAD rs1251106822, REVEL 0.75, CADD 27.20
- D50Y (p.Asp50Tyr), NCI-TCGA Cosmic COSV5971, cosmic curated COSV59714, Variant assessed as somatic; moderate impact.
- K51I (p.Lys51Ile), ESP rs370668897, ExAC rs370668897, TOPMed rs370668897, gnomAD rs370668897
- K51T (p.Lys51Thr), cosmic curated COSV59715, ESP rs370668897, ExAC rs370668897, TOPMed rs370668897, REVEL 0.83, CADD 26.70, Uncertain significance, not specified
- K51E (p.Lys51Glu), gnomAD 2-189795787-A-G, REVEL 0.81, CADD 27.10
- I52V (p.Ile52Val), gnomAD rs1463526642, REVEL 0.57, CADD 22.50
- I52I (p.Ile52Ile), rs972153044, gnomAD 2-189795792-T-C, CADD 10.40
- E53E (p.Glu53Glu), rs2106232968, gnomAD 2-189795795-G-A, CADD 8.39
- V54M (p.Val54Met), Ensembl rs2106232986, REVEL 0.87, CADD 25.40
- V54V (p.Val54Val), gnomAD 2-189795798-G-T, CADD 1.57
- R55* (p.Arg55Ter), cosmic curated COSV59721, ESP rs375147123, ExAC rs375147123, TOPMed rs375147123, CADD 37.00
- R55Q (p.Arg55Gln), cosmic curated COSV10968, gnomAD rs1376121914, REVEL 0.59, CADD 28.30
- D56G (p.Asp56Gly), ESP rs377024581, ExAC rs377024581, TOPMed rs377024581, gnomAD rs377024581, REVEL 0.96, CADD 28.70
- D56H (p.Asp56His), Ensembl rs2106233047, REVEL 0.98, CADD 27.00
- N57D (p.Asn57Asp), gnomAD rs1168215654, REVEL 0.70, CADD 26.00
- N57Y (p.Asn57Tyr), gnomAD 2-189795805-A-T, REVEL 0.94, CADD 26.20
- N57N (p.Asn57Asn), rs756254396, gnomAD 2-189795807-C-T, CADD 7.34
- G58E (p.Gly58Glu), cosmic curated COSV10520, ExAC rs773700771, gnomAD rs773700771, REVEL 0.99, CADD 26.30
- G58R (p.Gly58Arg), rs772427166, NCI-TCGA Cosmic COSV5971, cosmic curated COSV59715, ExAC rs772427166, REVEL 0.99, CADD 27.20, Variant assessed as somatic; moderate impact.
- G58V (p.Gly58Val), gnomAD 2-189795809-G-T, REVEL 0.99, CADD 26.00
- G58G (p.Gly58Gly), rs143323454, gnomAD 2-189795810-G-T, CADD 7.18
- E59G (p.Glu59Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E59K (p.Glu59Lys), rs587778608, ClinGen CA161497, ClinVar RCV000121814, ClinVar RCV005638440, REVEL 0.19, CADD 19.80, Likely benign, not provided
- E59* (p.Glu59Ter), gnomAD 2-189795811-G-T, CADD 36.00
- E59Q (p.Glu59Gln), gnomAD 2-189795811-G-C, REVEL 0.14, CADD 17.90
- E59A (p.Glu59Ala), gnomAD 2-189795812-A-C, REVEL 0.10, CADD 19.40
- E59E (p.Glu59Glu), rs1324848795, gnomAD 2-189795813-G-A, CADD 4.32
- G60D (p.Gly60Asp), gnomAD rs1298812483, REVEL 0.99, CADD 26.60
- G60S (p.Gly60Ser), TOPMed rs1040600809, gnomAD rs1040600809, REVEL 0.98, CADD 27.10
- I61M (p.Ile61Met), NCI-TCGA Cosmic COSV1005, cosmic curated COSV10057, REVEL 0.68, CADD 22.60, Variant assessed as somatic; moderate impact.
- I61V (p.Ile61Val), gnomAD rs1330142638, REVEL 0.40, CADD 17.70
- K62E (p.Lys62Glu), Ensembl rs2049306445, REVEL 0.45, CADD 25.40
- K62K (p.Lys62Lys), gnomAD 2-189795822-G-A, CADD 8.84
- A63D (p.Ala63Asp), Ensembl rs2106233250
- A63T (p.Ala63Thr), Ensembl rs2106233243
- A63V (p.Ala63Val), Ensembl rs2106233250, REVEL 0.36, CADD 21.80
- V64I (p.Val64Ile), TOPMed rs1401716323, gnomAD rs1401716323, REVEL 0.25, CADD 4.56
- V64F (p.Val64Phe), gnomAD 2-189795826-G-T, REVEL 0.35, CADD 14.10
- V64A (p.Val64Ala), gnomAD 2-189795827-T-C, REVEL 0.13, CADD 7.69
- D65V (p.Asp65Val), Ensembl rs2106233278
- D65D (p.Asp65Asp), gnomAD 2-189795831-T-C, CADD 11.50
- A66T (p.Ala66Thr), Ensembl rs2049307101, REVEL 0.40, CADD 18.40
- P67A (p.Pro67Ala), ExAC rs777322683, gnomAD rs777322683
- P67L (p.Pro67Leu), Ensembl rs2106233322
- P67S (p.Pro67Ser), ExAC rs777322683, gnomAD rs777322683, REVEL 0.32, CADD 21.40
- V68I (p.Val68Ile), gnomAD rs1252188244, REVEL 0.50, CADD 25.80
- M69I (p.Met69Ile), TOPMed rs1344960114, gnomAD rs1344960114, REVEL 0.62, CADD 26.60
- M69L (p.Met69Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A70S (p.Ala70Ser), ExAC rs753676547, TOPMed rs753676547, gnomAD rs753676547, REVEL 0.63, CADD 26.50
- A70T (p.Ala70Thr), cosmic curated COSV59716, ExAC rs753676547, TOPMed rs753676547, gnomAD rs753676547, REVEL 0.54, CADD 27.40
- M71I (p.Met71Ile), TOPMed rs1172365010, gnomAD rs1172365010, REVEL 0.31, CADD 15.70
- M71V (p.Met71Val), ExAC rs763541657, gnomAD rs763541657, REVEL 0.33, CADD 4.77
- K72N (p.Lys72Asn), Ensembl rs2106233426
- K72R (p.Lys72Arg), gnomAD 2-189795851-A-G, REVEL 0.23, CADD 22.90
- Y73F (p.Tyr73Phe), NCI-TCGA Cosmic COSV1005, cosmic curated COSV10057, Variant assessed as somatic; moderate impact.
Public PMS1 analysis runs
- PMS1 analysis run — PMS1 (1,649 variants) — completed 2026-08-22