MLH1 (DNA mismatch repair protein Mlh1) variants and mutations
MLH1 (also known as DNA mismatch repair protein Mlh1) is a human protein-coding gene encoding a DNA mismatch repair protein. The protein partners with PMS2 to form MutL alpha, a core complex in post-replicative DNA mismatch repair. By helping correct copying errors in DNA, MLH1 protects genome stability, and inherited MLH1 variants are a major cause of Lynch syndrome. This analysis covers 3,606 MLH1 variants and mutations. Of these, 96% have computational variant effect predictions. Disease context includes Lynch syndrome, mismatch repair cancer syndrome 1, and colorectal cancer. Example MLH1 variants include M1I, M1K, and M1L.
Variant analysis overview
- Gene: MLH1
- Protein: DNA mismatch repair protein Mlh1
- UniProt accession: P40692
- Organism: Homo sapiens
- Variants analyzed: 3606
- Variant scope: all variants
- Completed: 2026-05-15
Variant and mutation evidence
- Variant composition: 3,506 unspecified-consequence records; 69 synonymous variants; 18 missense variants; 7 splice-region variants; 5 frameshift variants; 1 substitution
- Prediction scores: 3,450 variants have prediction scores (96% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Lynch syndrome, mismatch repair cancer syndrome 1, colorectal cancer, Muir-Torre syndrome, colon carcinoma, Constitutional mismatch repair deficiency syndrome, colonic neoplasm, malignant colon neoplasm, hereditary nonpolyposis colon cancer, endometrial carcinoma, neoplasm, hereditary neoplastic syndrome.
Protein structure and variant hotspots
- Protein features: 4 binding sites; 6 post-translational modification sites.
- PTM context: 29 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, PharmGKB, MaveDB, LitVar.
Notable MLH1 variants
Examples include M1I, M1K, M1L, M1R, M1T, M1V, S2A, S2P. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs72481822, ClinGen CA010267, ClinVar RCV000075700, ClinVar RCV000215403, ESM-1b 1.00, AlphaMissense 0.55, Likely pathogenic, Lynch syndrome 1
- M1K (p.Met1Lys), rs111052004, ClinGen CA009594, ClinVar RCV000075620, ClinVar RCV003362685, ESM-1b 1.00, AlphaMissense 0.71, Uncertain significance, Lynch syndrome
- M1L (p.Met1Leu), rs587778967, ClinGen CA352059785, ClinVar RCV001644559, ClinVar RCV002421236, ESM-1b 1.00, AlphaMissense 0.18, Uncertain significance, Hereditary cancer-predisposing syndrome
- M1R (p.Met1Arg), rs111052004, ClinGen CA009606, ClinVar RCV000075622, ClinVar RCV002433578, ESM-1b 1.00, AlphaMissense 0.64, Uncertain significance, Lynch syndrome 1
- M1T (p.Met1Thr), rs111052004, ClinGen CA009600, ClinVar RCV000075621, ClinVar RCV001800370, ESM-1b 1.00, AlphaMissense 0.66, Likely benign, Lynch syndrome 1
- M1V (p.Met1Val), rs587778967, ClinGen CA008127, ClinVar RCV000075477, ClinVar RCV000629832, ESM-1b 1.00, AlphaMissense 0.15, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- S2A (p.Ser2Ala), rs1448308275, ClinGen CA352059811, ClinVar RCV001071771, ClinVar RCV001093665, REVEL 0.39, ESM-1b 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- S2P (p.Ser2Pro), TOPMed rs1448308275, gnomAD rs1448308275, ESM-1b 0.00, AlphaMissense 0.13, Uncertain significance
- S2T (p.Ser2Thr), TOPMed rs1448308275, gnomAD rs1448308275, ESM-1b 0.00, AlphaMissense 0.11, Uncertain significance
- S2* (p.Ser2Ter), rs587779029, ClinGen CA011228, ClinVar RCV000075784, ClinVar RCV003456001, MutPred 0.45, Pathogenic
- S2L (p.Ser2Leu), rs587779029, ClinGen CA011236, ClinVar RCV000160548, ClinVar RCV000221241, REVEL 0.48, ESM-1b 0.28, Conflicting interpretations, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- S2W (p.Ser2Trp), rs587779029, ClinGen CA352059834, ClinVar RCV001758476, ExAC rs587779029, REVEL 0.58, ESM-1b 1.00, Uncertain significance, not provided
- S2S (p.Ser2Ser), rs757950578, gnomAD 3-36993553-G-C, CADD 13.50
- F3C (p.Phe3Cys), Ensembl rs2125693369, REVEL 0.42, ESM-1b 0.00
- F3L (p.Phe3Leu), rs878853790, ClinGen CA10582150, ClinVar RCV000234545, ClinVar RCV000574682, REVEL 0.35, ESM-1b 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome
- F3S (p.Phe3Ser), gnomAD 3-36993555-T-C, REVEL 0.34, ESM-1b 0.00
- F3F (p.Phe3Phe), gnomAD 3-36993556-C-T, CADD 4.50
- V4A (p.Val4Ala), NCI-TCGA Cosmic COSV5161, ESM-1b 0.00, AlphaMissense 0.08, Variant assessed as somatic; moderate impact.
- V4E (p.Val4Glu), Ensembl rs2125693417, ESM-1b 0.00, AlphaMissense 0.17
- V4G (p.Val4Gly), Ensembl rs2125693417, REVEL 0.45, ESM-1b 0.00
- V4L (p.Val4Leu), rs1559500060, ClinGen CA352060308, ClinVar RCV001304319, Ensembl rs1559500060, REVEL 0.36, ESM-1b 0.00, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- V4M (p.Val4Met), rs1559500060, ClinGen CA352060321, ClinVar RCV000775325, ClinVar RCV003320740, REVEL 0.31, ESM-1b 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- V4V (p.Val4Val), rs864622700, gnomAD 3-36993559-G-T, CADD 7.13
- A5G (p.Ala5Gly), Ensembl rs878853779, ESM-1b 0.00, AlphaMissense 0.21, Uncertain significance
- A5P (p.Ala5Pro), rs1389945622, ClinGen CA352060369, ClinVar RCV000565132, ClinVar RCV003593994, REVEL 0.48, ESM-1b 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- A5S (p.Ala5Ser), rs1389945622, ClinGen CA352060370, ClinVar RCV001011372, gnomAD rs1389945622, ESM-1b 0.00, AlphaMissense 0.16, Uncertain significance, Hereditary cancer-predisposing syndrome
- A5T (p.Ala5Thr), rs1389945622, ClinGen CA352060368, ClinVar RCV002389245, gnomAD rs1389945622, ESM-1b 0.00, AlphaMissense 0.33, Uncertain significance, Hereditary cancer-predisposing syndrome
- A5V (p.Ala5Val), rs878853779, ClinGen CA10582151, ClinVar RCV000225822, ClinVar RCV001836759, REVEL 0.53, ESM-1b 0.00, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- A5A (p.Ala5Ala), rs2080886445, gnomAD 3-36993562-A-G, CADD 12.40
- A5D (p.Ala5Asp), rs2125736835, gnomAD 3-37001041-C-A, REVEL 0.27, CADD 11.20
- G6A (p.Gly6Ala), TOPMed rs2080887074, ESM-1b 1.00, AlphaMissense 0.21, Uncertain significance
- G6E (p.Gly6Glu), rs2080887074, ClinGen CA352060416, ClinVar RCV002407886, ClinVar RCV004808323, ESM-1b 1.00, AlphaMissense 0.71, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- G6R (p.Gly6Arg), rs1366752604, gnomAD rs1366752604, ClinGen CA090872, ClinVar RCV002406301, ESM-1b 1.00, AlphaMissense 0.73, Uncertain significance, Hereditary cancer-predisposing syndrome
- G6V (p.Gly6Val), rs2080887074, ClinGen CA352060436, ClinVar RCV002407891, ClinVar RCV003465737, REVEL 0.67, ESM-1b 1.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Colorectal cancer, hereditary nonpolypo
- G6W (p.Gly6Trp), rs1366752604, ClinGen CA352060401, ClinVar RCV002308973, ClinVar RCV002400445, REVEL 0.79, ESM-1b 1.00, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome
- G6G (p.Gly6Gly), rs786202312, gnomAD 3-36993565-G-C, CADD 8.87
- V7A (p.Val7Ala), rs755402059, ClinGen CA352060447, ClinVar RCV003594767, ClinVar RCV004011348, ESM-1b 0.00, AlphaMissense 0.26, Uncertain significance, Lynch syndrome; Hereditary nonpolyposis colorectal neoplasms
- V7F (p.Val7Phe), rs730881746, ClinGen CA008120, ClinVar RCV000160549, ClinVar RCV000703809, REVEL 0.67, ESM-1b 1.00, Conflicting interpretations, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- V7G (p.Val7Gly), ExAC rs755402059, gnomAD rs755402059, REVEL 0.72, ESM-1b 1.00, Uncertain significance
- V7I (p.Val7Ile), ExAC rs730881746, TOPMed rs730881746, gnomAD rs730881746, ESM-1b 0.32, AlphaMissense 0.07, Uncertain significance, Hereditary cancer-predisposing syndrome
- V7L (p.Val7Leu), rs730881746, ClinGen CA352060442, ClinVar RCV003172139, ESM-1b 1.00, AlphaMissense 0.26, Uncertain significance, Hereditary cancer-predisposing syndrome
- V7V (p.Val7Val), rs781725830, gnomAD 3-36993568-T-C, CADD 14.10
- I8F (p.Ile8Phe), rs1313488508, ClinGen CA352060468, ClinVar RCV002428468, ClinVar RCV003098791, ESM-1b 1.00, AlphaMissense 0.97, Uncertain significance, not provided; Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-pr
- I8L (p.Ile8Leu), rs1313488508, ClinGen CA352060456, ClinVar RCV002446298, ClinVar RCV003759721, REVEL 0.85, ESM-1b 1.00, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- I8M (p.Ile8Met), rs748406142, ClinGen CA352060477, ClinVar RCV001061739, ClinVar RCV002429695, REVEL 0.82, ESM-1b 1.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- I8R (p.Ile8Arg), rs2470598661, ClinGen CA2586971866, ClinVar RCV003452387, Pathogenic
- I8S (p.Ile8Ser), Ensembl rs2125693622, ESM-1b 1.00, AlphaMissense 0.99
- I8T (p.Ile8Thr), rs2125693622, ClinGen CA352060472, ClinVar RCV003477297, ESM-1b 1.00, AlphaMissense 1.00, Uncertain significance, not provided
- I8V (p.Ile8Val), rs1313488508, ClinGen CA352060461, ClinVar RCV001183496, gnomAD rs1313488508, ESM-1b 1.00, AlphaMissense 0.75, Uncertain significance, Hereditary cancer-predisposing syndrome
- I8N (p.Ile8Asn), gnomAD 3-36993570-T-A, REVEL 0.90, ESM-1b 1.00
- I8I (p.Ile8Ile), rs748406142, gnomAD 3-36993571-T-A, CADD 13.20
- R9* (p.Arg9Ter), rs869312767, ClinGen CA357820, ClinVar RCV000210198, ClinVar RCV000820368, Pathogenic
- R9G (p.Arg9Gly), rs587779000, ClinGen CA72786435, ClinVar RCV001177312, ClinVar RCV002559722, ESM-1b 1.00, AlphaMissense 0.63, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- R9H (p.Arg9His), rs2125693660, ClinGen CA2573136313, ClinVar RCV001912306, Ensembl rs2125693660, ESM-1b 0.00, AlphaMissense 0.17, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- R9L (p.Arg9Leu), gnomAD rs1274810165, REVEL 0.66, ESM-1b 1.00, Uncertain significance
- R9P (p.Arg9Pro), gnomAD rs1274810165, REVEL 0.84, ESM-1b 1.00, Uncertain significance
- R9Q (p.Arg9Gln), rs1274810165, ClinGen CA352060479, NCI-TCGA Cosmic COSV5162, ClinVar RCV000698909, REVEL 0.55, ESM-1b 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- R9W (p.Arg9Trp), rs587779000, ClinGen CA009458, ClinVar RCV000579430, ClinVar RCV000822650, REVEL 0.86, ESM-1b 1.00, Uncertain significance, Colorectal cancer, hereditary nonpolyposis, type 2; Hereditary cancer-predisposi
- R9R (p.Arg9Arg), rs759680369, gnomAD 3-36993574-G-T, CADD 15.30
- R10G (p.Arg10Gly), rs1193754562, ClinGen CA352060490, ClinVar RCV000506936, ClinVar RCV000580223, REVEL 0.82, ESM-1b 1.00, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- R10L (p.Arg10Leu), rs777971423, ClinGen CA352060509, ClinVar RCV000580818, ClinVar RCV001030559, REVEL 0.75, ESM-1b 1.00, Uncertain significance, Hereditary breast ovarian cancer syndrome; Hereditary nonpolyposis colorectal ne
- R10Q (p.Arg10Gln), rs777971423, ClinGen CA034460, ClinVar RCV000221934, ClinVar RCV000690244, REVEL 0.75, ESM-1b 1.00, Uncertain significance, not specified; Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-p
- R10W (p.Arg10Trp), rs1193754562, ClinGen CA352060492, ClinVar RCV000580563, ClinVar RCV001048967, REVEL 0.85, ESM-1b 1.00, Uncertain significance, not specified; Colorectal cancer, hereditary nonpolyposis, type 2; Hereditary no
- R10R (p.Arg10Arg), rs1193754562, gnomAD 3-36993575-C-A, CADD 15.30
- L11M (p.Leu11Met), Ensembl rs864622596, ESM-1b 1.00, AlphaMissense 0.94, Likely benign
- L11P (p.Leu11Pro), rs1575375926, ClinGen CA352060541, ClinVar RCV001238892, Ensembl rs1575375926, ESM-1b 1.00, AlphaMissense 1.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- L11R (p.Leu11Arg), rs1575375926, ClinGen CA352060544, ClinVar RCV001041179, ClinVar RCV002454292, ESM-1b 1.00, AlphaMissense 0.99, Uncertain significance, Hereditary cancer-predisposing syndrome
- L11V (p.Leu11Val), rs864622596, ClinGen CA350564, ClinVar RCV000206543, ClinVar RCV003417746, REVEL 0.81, ESM-1b 1.00, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- D12* (p.Asp12Ter), rs2470599366, ClinGen CA2580069384, ClinVar RCV002452070, Pathogenic
- D12E (p.Asp12Glu), rs587782181, ClinGen CA009931, ClinVar RCV000130802, ClinVar RCV000804813, REVEL 0.60, ESM-1b 0.06, Uncertain significance, Mismatch repair cancer syndrome 1; Muir-Torré syndrome; Colorectal cancer, hered
- D12G (p.Asp12Gly), rs1553637200, ClinGen CA352060557, ClinVar RCV000630230, Ensembl rs1553637200, ESM-1b 1.00, AlphaMissense 0.35, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- D12N (p.Asp12Asn), rs749548566, ClinGen CA034988, ClinVar RCV000214109, ExAC rs749548566, REVEL 0.69, ESM-1b 1.00, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- D12V (p.Asp12Val), Ensembl rs1553637200, ESM-1b 1.00, AlphaMissense 0.68, Uncertain significance
- D12Y (p.Asp12Tyr), ExAC rs749548566, gnomAD rs749548566, REVEL 0.87, ESM-1b 1.00, Uncertain significance
- D12D (p.Asp12Asp), rs587782181, gnomAD 3-36993583-C-T, CADD 14.50
- E13* (p.Glu13Ter), rs587779008, ClinGen CA010022, ClinVar RCV000075677, ClinVar RCV000162469, MutPred 0.36, Pathogenic
- E13D (p.Glu13Asp), rs587779013, ClinGen CA2580614169, ClinVar RCV002366409, REVEL 0.73, CADD 24.50, Uncertain significance, Hereditary cancer-predisposing syndrome
- E13G (p.Glu13Gly), rs1575376099, ClinGen CA352060582, ClinVar RCV001021384, ClinVar RCV003758987, ESM-1b 1.00, AlphaMissense 0.49, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- E13K (p.Glu13Lys), rs587779008, ClinGen CA010013, NCI-TCGA Cosmic COSV5161, NCI-TCGA Cosmic COSV5162, REVEL 0.78, ESM-1b 0.88, Conflicting interpretations, Hereditary nonpolyposis colorectal neoplasms; Breast and/or ovarian cancer; Here
- E13Q (p.Glu13Gln), rs587779008, ClinGen CA72786491, ClinVar RCV000563924, ClinVar RCV001251349, REVEL 0.67, ESM-1b 1.00, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- T14A (p.Thr14Ala), rs2125693873, ClinGen CA352060615, ClinVar RCV001867360, Ensembl rs2125693873, ESM-1b 0.00, AlphaMissense 0.07, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- T14I (p.Thr14Ile), rs774363593, ClinGen CA035624, ClinVar RCV000456258, ClinVar RCV000478685, REVEL 0.55, ESM-1b 0.23, Conflicting interpretations, Hereditary nonpolyposis colorectal neoplasms; Lynch syndrome; Hereditary cancer
- T14K (p.Thr14Lys), rs774363593, ClinGen CA352060620, ClinVar RCV002327849, ExAC rs774363593, ESM-1b 1.00, AlphaMissense 0.18, Uncertain significance, Hereditary cancer-predisposing syndrome
- T14R (p.Thr14Arg), rs774363593, ClinGen CA352060647, ClinVar RCV003358382, ExAC rs774363593, REVEL 0.59, ESM-1b 1.00, Uncertain significance, Hereditary cancer-predisposing syndrome
- T14T (p.Thr14Thr), rs369737664, gnomAD 3-36993589-A-C, CADD 11.50
- V15A (p.Val15Ala), rs864622396, ClinGen CA349380, ClinVar RCV000205194, ClinVar RCV001022596, REVEL 0.83, ESM-1b 1.00, Uncertain significance, Hereditary cancer-predisposing syndrome
- V15G (p.Val15Gly), rs864622396, ClinGen CA352060683, ClinVar RCV003760774, ESM-1b 1.00, AlphaMissense 0.97, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- V15L (p.Val15Leu), rs876660301, ClinGen CA352060666, ClinVar RCV000698872, Ensembl rs876660301, REVEL 0.75, ESM-1b 1.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- V15M (p.Val15Met), rs876660301, ClinGen CA10578192, ClinVar RCV000221816, ClinVar RCV000479027, REVEL 0.75, ESM-1b 1.00, Conflicting interpretations, Hereditary nonpolyposis colorectal neoplasms; not provided; Hereditary cancer-pr
- V15V (p.Val15Val), rs768409958, gnomAD 3-36993592-G-T, CADD 14.60
- V16G (p.Val16Gly), rs1553637237, ClinGen CA352060695, ClinVar RCV000522288, ClinVar RCV000546291, REVEL 0.89, ESM-1b 1.00, Uncertain significance, Lynch syndrome; Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer
- V16L (p.Val16Leu), rs776643257, ClinGen CA036168, ClinVar RCV000554111, ClinVar RCV000565039, REVEL 0.85, ESM-1b 1.00, Conflicting interpretations, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- V16M (p.Val16Met), rs776643257, ClinGen CA10578193, NCI-TCGA Cosmic COSV9921, ClinVar RCV000214613, REVEL 0.88, ESM-1b 1.00, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- V16V (p.Val16Val), rs2125693986, gnomAD 3-36993595-G-A, CADD 16.40
- N17D (p.Asn17Asp), Ensembl rs2125693995, REVEL 0.82, ESM-1b 1.00
- N17I (p.Asn17Ile), rs1403203490, ClinGen CA352060720, ClinVar RCV002335982, gnomAD rs1403203490, ESM-1b 1.00, AlphaMissense 0.98, Uncertain significance, Hereditary cancer-predisposing syndrome
- N17K (p.Asn17Lys), rs761498953, ClinGen CA352060728, ClinVar RCV004017020, ExAC rs761498953, ESM-1b 1.00, AlphaMissense 0.99, Uncertain significance, Lynch syndrome
- N17S (p.Asn17Ser), rs1403203490, ClinGen CA352060717, ClinVar RCV000571321, ClinVar RCV001298949, ESM-1b 1.00, AlphaMissense 0.43, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- N17Y (p.Asn17Tyr), Ensembl rs2125693995, REVEL 0.90, ESM-1b 1.00
- N17N (p.Asn17Asn), rs761498953, gnomAD 3-36993598-C-T, CADD 12.70
- R18C (p.Arg18Cys), rs367654552, ClinGen CA010776, NCI-TCGA Cosmic COSV9921, ClinVar RCV000121355, REVEL 0.83, ESM-1b 1.00, Conflicting interpretations, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- R18G (p.Arg18Gly), rs367654552, ClinGen CA036379, ClinVar RCV000568925, ClinVar RCV000685595, REVEL 0.84, ESM-1b 1.00, Uncertain significance, Lynch syndrome; Colorectal cancer, hereditary nonpolyposis, type 2; Hereditary c
- R18H (p.Arg18His), rs1553637254, ClinGen CA352060756, ClinVar RCV000564188, ClinVar RCV001069605, ESM-1b 1.00, AlphaMissense 0.86, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- R18S (p.Arg18Ser), ESP rs367654552, ExAC rs367654552, gnomAD rs367654552, REVEL 0.82, ESM-1b 1.00, Uncertain significance, Mismatch repair cancer syndrome 1; Muir-Torré syndrome; Colorectal cancer, hered
- R18L (p.Arg18Leu), gnomAD 3-36993600-G-T, REVEL 0.85, ESM-1b 1.00
- I19F (p.Ile19Phe), rs63750648, ClinGen CA011026, ClinVar RCV000075763, ClinVar RCV000162610, ESM-1b 1.00, AlphaMissense 0.99, Pathogenic, Lynch syndrome 1
- I19L (p.Ile19Leu), rs63750648, ClinGen CA352060766, ClinVar RCV001024309, ClinVar RCV002551891, ESM-1b 1.00, AlphaMissense 0.95, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- I19M (p.Ile19Met), rs762647509, ClinGen CA352060791, ClinVar RCV001185639, ExAC rs762647509, ESM-1b 1.00, AlphaMissense 0.93, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- I19N (p.Ile19Asn), rs2125694114, ClinGen CA352060774, ClinVar RCV002347565, Ensembl rs2125694114, ESM-1b 1.00, AlphaMissense 1.00, Uncertain significance, Hereditary cancer-predisposing syndrome
- I19S (p.Ile19Ser), Ensembl rs2125694114, REVEL 0.92, ESM-1b 1.00, Uncertain significance, in LYNCH2
- I19V (p.Ile19Val), TOPMed rs63750648, gnomAD rs63750648, REVEL 0.78, ESM-1b 1.00, Pathogenic, in LYNCH2
- A20E (p.Ala20Glu), gnomAD rs1391455682, ESM-1b 1.00, AlphaMissense 1.00, Uncertain significance
- A20G (p.Ala20Gly), rs1391455682, ClinGen CA352060817, ClinVar RCV004522903, gnomAD rs1391455682, ESM-1b 1.00, AlphaMissense 0.96, Uncertain significance, Hereditary cancer-predisposing syndrome
- A20P (p.Ala20Pro), rs1553637262, ClinGen CA352060807, ClinVar RCV001937340, Ensembl rs1553637262, ESM-1b 1.00, AlphaMissense 1.00, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- A20S (p.Ala20Ser), Ensembl rs1553637262, ESM-1b 1.00, AlphaMissense 0.66, Uncertain significance
- A20T (p.Ala20Thr), rs1553637262, ClinGen CA352060802, ClinVar RCV000579881, Ensembl rs1553637262, ESM-1b 1.00, AlphaMissense 0.98, Uncertain significance, Hereditary cancer-predisposing syndrome
- A20V (p.Ala20Val), rs1391455682, ClinGen CA352060822, ClinVar RCV001177268, ClinVar RCV001819880, REVEL 0.87, ESM-1b 1.00, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- A20A (p.Ala20Ala), rs2080897097, gnomAD 3-36993607-G-T, CADD 15.30
- A21P (p.Ala21Pro), rs2080897397, ClinGen CA352060832, ClinVar RCV002016807, Ensembl rs2080897397, ESM-1b 1.00, AlphaMissense 1.00, Likely pathogenic, Hereditary nonpolyposis colorectal neoplasms
- A21T (p.Ala21Thr), rs2080897397, ClinGen CA352060839, ClinVar RCV002353851, REVEL 0.90, ESM-1b 1.00, Uncertain significance, Hereditary cancer-predisposing syndrome
- A21E (p.Ala21Glu), rs63750706, ClinGen CA011283, ClinVar RCV000075786, ClinVar RCV000811318, ESM-1b 1.00, AlphaMissense 1.00, Pathogenic, Lynch syndrome
- A21G (p.Ala21Gly), rs63750706, ClinGen CA352060842, ClinVar RCV003759230, ESM-1b 1.00, AlphaMissense 0.97, Likely pathogenic, Hereditary nonpolyposis colorectal neoplasms
- A21S (p.Ala21Ser), rs2080897397, ClinGen CA352060835, ClinVar RCV001069082, ClinVar RCV002355096, ESM-1b 1.00, AlphaMissense 0.86, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- A21V (p.Ala21Val), rs63750706, ClinGen CA011295, ClinVar RCV000075787, ClinVar RCV001269890, ESM-1b 1.00, AlphaMissense 0.99, Pathogenic, Lynch syndrome 1
- A21A (p.Ala21Ala), rs1553637274, gnomAD 3-36993610-G-A, CADD 15.90
- G22A (p.Gly22Ala), rs41295280, ClinGen CA011425, ClinVar RCV000075796, ClinVar RCV000115484, REVEL 0.91, ESM-1b 1.00, Benign, Lynch syndrome
- G22E (p.Gly22Glu), rs41295280, ClinGen CA352060859, ClinVar RCV002638286, ClinVar RCV003162082, ESM-1b 1.00, AlphaMissense 1.00, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- G22R (p.Gly22Arg), rs2125694239, ClinGen CA352060852, ClinVar RCV004522904, Ensembl rs2125694239, REVEL 0.93, ESM-1b 1.00, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- G22V (p.Gly22Val), rs41295280, ClinGen CA352060856, ClinVar RCV001212800, ESP rs41295280, ESM-1b 1.00, AlphaMissense 0.99, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- G22G (p.Gly22Gly), rs2125694260, gnomAD 3-36993613-G-A, CADD 14.80
- E23* (p.Glu23Ter), rs63750823, ClinGen CA011669, ClinVar RCV000075822, ClinVar RCV000160551, MutPred 0.86, Pathogenic
- E23A (p.Glu23Ala), rs750969880, ClinGen CA352060865, ClinVar RCV001025777, ExAC rs750969880, ESM-1b 1.00, AlphaMissense 0.99, Uncertain significance, Hereditary cancer-predisposing syndrome
- E23D (p.Glu23Asp), rs63750555, ClinGen CA011736, ClinVar RCV000411283, ClinVar RCV001025892, ESM-1b 1.00, AlphaMissense 1.00, Likely pathogenic, Hereditary cancer-predisposing syndrome
- E23G (p.Glu23Gly), rs750969880, ClinGen CA037916, ClinVar RCV001025779, ClinVar RCV001366114, REVEL 0.92, ESM-1b 1.00, Uncertain significance, Breast and/or ovarian cancer; Hereditary nonpolyposis colorectal neoplasms; Here
- E23K (p.Glu23Lys), rs63750823, ClinGen CA011662, ClinVar RCV001221485, ClinVar RCV004019105, REVEL 0.94, ESM-1b 1.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- E23E (p.Glu23Glu), rs63750555, gnomAD 3-36993616-A-G, CADD 15.40
- V24A (p.Val24Ala), rs754533438, ClinGen CA352060889, ClinVar RCV002051237, ClinVar RCV004808137, ESM-1b 1.00, AlphaMissense 1.00, Uncertain significance, Lynch syndrome; not provided; Hereditary nonpolyposis colorectal neoplasms
- V24D (p.Val24Asp), ExAC rs754533438, gnomAD rs754533438, ESM-1b 1.00, AlphaMissense 1.00, Uncertain significance
- V24F (p.Val24Phe), rs1348994712, ClinGen CA352060882, ClinVar RCV001964287, Ensembl rs1348994712, ESM-1b 1.00, AlphaMissense 0.99, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- V24G (p.Val24Gly), rs754533438, ClinGen CA038025, ClinVar RCV001799420, ExAC rs754533438, ESM-1b 1.00, AlphaMissense 0.99, Uncertain significance, Breast and/or ovarian cancer
- V24I (p.Val24Ile), rs1348994712, ClinGen CA352060879, ClinVar RCV001292948, ClinVar RCV001863175, ESM-1b 0.00, AlphaMissense 0.12, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Colorectal cancer, hereditary nonp
- V24L (p.Val24Leu), Ensembl rs1348994712, REVEL 0.79, ESM-1b 1.00, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- I25F (p.Ile25Phe), rs63749838, ClinGen CA011880, ClinVar RCV000075834, UniProt VAR 043385, ESM-1b 1.00, AlphaMissense 0.99, Likely pathogenic, Lynch syndrome
- I25M (p.Ile25Met), ExAC rs753317868, gnomAD rs753317868, ESM-1b 1.00, AlphaMissense 0.91, Likely benign, in LYNCH2
- I25S (p.Ile25Ser), rs63750514, ClinGen CA352060907, ClinVar RCV003758388, ESM-1b 1.00, AlphaMissense 1.00, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- I25T (p.Ile25Thr), rs63750514, ClinGen CA011945, ClinVar RCV001961868, ClinVar RCV003299072, REVEL 0.93, ESM-1b 1.00, Uncertain significance, MLH1-related disorder; Hereditary nonpolyposis colorectal neoplasms; Hereditary
- I25V (p.Ile25Val), rs63749838, ClinGen CA16617881, ClinVar RCV000481596, ClinVar RCV001026386, REVEL 0.69, ESM-1b 0.00, Uncertain significance, not provided; Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-pr
- I25N (p.Ile25Asn), gnomAD 3-36993621-T-A, REVEL 0.92, ESM-1b 1.00
- I25I (p.Ile25Ile), rs753317868, gnomAD 3-36993622-C-T, CADD 13.90
- Q26* (p.Gln26Ter), rs63749827, ClinGen CA011979, ClinVar RCV000075838, ClinVar RCV000520796, Pathogenic
- Q26E (p.Gln26Glu), Ensembl rs63749827, ESM-1b 1.00, AlphaMissense 0.61, Pathogenic
- Q26H (p.Gln26His), rs2080901714, ClinGen CA352060928, ClinVar RCV001211630, ClinVar RCV004010683, ESM-1b 1.00, AlphaMissense 0.79, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Lynch syndrome
- Q26K (p.Gln26Lys), rs63749827, ClinGen CA352060914, ClinVar RCV003758374, ESM-1b 1.00, AlphaMissense 0.88, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- Q26L (p.Gln26Leu), Ensembl rs1553637312, ESM-1b 1.00, AlphaMissense 0.55, Uncertain significance
- Q26P (p.Gln26Pro), rs1553637312, ClinGen CA352060919, ClinVar RCV000542409, ClinVar RCV001026821, ESM-1b 1.00, AlphaMissense 0.79, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- Q26R (p.Gln26Arg), rs1553637312, ClinGen CA352060922, ClinVar RCV000554849, ClinVar RCV004568714, ESM-1b 1.00, AlphaMissense 0.84, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- R27G (p.Arg27Gly), rs756398627, ClinGen CA352060934, ClinVar RCV000580638, ClinVar RCV000696487, ESM-1b 1.00, AlphaMissense 0.96, Uncertain significance, Hereditary cancer-predisposing syndrome
- R27P (p.Arg27Pro), rs138705565, ClinGen CA012479, ClinVar RCV000030232, ClinVar RCV000662420, ESM-1b 1.00, AlphaMissense 1.00, Uncertain significance
- R27Q (p.Arg27Gln), rs138705565, ClinGen CA038485, ClinVar RCV000197307, ClinVar RCV000573727, REVEL 0.88, ESM-1b 1.00, Conflicting interpretations, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- R27W (p.Arg27Trp), rs756398627, ClinGen CA038419, ClinVar RCV000570479, ClinVar RCV000822281, REVEL 0.79, ESM-1b 1.00, Conflicting interpretations, Colorectal cancer, hereditary nonpolyposis, type 2; Hereditary cancer-predisposi
- P28A (p.Pro28Ala), Ensembl rs1559500757, ESM-1b 1.00, AlphaMissense 0.85, Uncertain significance, in LYNCH2
- P28L (p.Pro28Leu), rs63750792, ClinGen CA012549, ClinVar RCV000075881, ClinVar RCV000160552, REVEL 0.85, ESM-1b 1.00, Pathogenic, Lynch syndrome
- P28Q (p.Pro28Gln), rs63750792, ClinGen CA352060955, ClinVar RCV002306317, ClinVar RCV002434636, ESM-1b 1.00, AlphaMissense 1.00, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- P28S (p.Pro28Ser), rs1559500757, ClinGen CA352060951, ClinVar RCV000771489, ClinVar RCV005092223, REVEL 0.88, ESM-1b 1.00, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- P28T (p.Pro28Thr), gnomAD 3-36993629-C-A, REVEL 0.87, ESM-1b 1.00
- P28P (p.Pro28Pro), rs1575376993, gnomAD 3-36993631-A-C, CADD 12.70
- A29D (p.Ala29Asp), rs63750216, ClinGen CA352060980, ClinVar RCV000774012, ClinVar RCV000817002, ESM-1b 1.00, AlphaMissense 0.95, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- A29G (p.Ala29Gly), rs63750216, ClinGen CA012745, ClinVar RCV000075896, ClinVar RCV000218998, ESM-1b 1.00, AlphaMissense 0.26, Pathogenic, Lynch syndrome
- A29P (p.Ala29Pro), Ensembl rs63750656, ESM-1b 1.00, AlphaMissense 0.82, Uncertain significance, Mismatch repair cancer syndrome 1; Muir-Torré syndrome; Colorectal cancer, hered
- A29S (p.Ala29Ser), rs63750656, ClinGen CA012662, ClinVar RCV000132377, ClinVar RCV000201970, ESM-1b 0.00, AlphaMissense 0.10, Pathogenic, Lynch syndrome 1
- A29T (p.Ala29Thr), Ensembl rs63750656, ESM-1b 1.00, AlphaMissense 0.23, Pathogenic, in LYNCH2
- A29V (p.Ala29Val), rs63750216, ClinVar RCV004574880, ESM-1b 0.76, AlphaMissense 0.19, Uncertain significance, Colorectal cancer, hereditary nonpolyposis, type 2
- N30D (p.Asn30Asp), rs2470602894, ClinGen CA352060999, ClinVar RCV002376042, ESM-1b 1.00, AlphaMissense 0.89, Uncertain significance, Hereditary cancer-predisposing syndrome
- N30I (p.Asn30Ile), rs2080903905, ClinGen CA352061013, ClinVar RCV001234633, Ensembl rs2080903905, ESM-1b 1.00, AlphaMissense 0.92, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- N30K (p.Asn30Lys), rs863224637, ClinGen CA352061018, ClinVar RCV001372351, TOPMed rs863224637, REVEL 0.74, ESM-1b 1.00, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- N30S (p.Asn30Ser), rs2080903905, ClinGen CA352061010, ClinVar RCV001187453, ClinVar RCV001210115, ESM-1b 1.00, AlphaMissense 0.13, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- N30T (p.Asn30Thr), NCI-TCGA TCGA novel, REVEL 0.81, ESM-1b 1.00, Variant assessed as somatic; moderate impact.
- A31C (p.Ala31Cys), rs63749994, ClinGen CA013075, ClinVar RCV000115487, ClinVar RCV000235172, ESM-1b 1.00, AlphaMissense 0.80, Conflicting interpretations, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- A31D (p.Ala31Asp), rs730882127, ClinGen CA352061044, ClinVar RCV002280603, ClinVar RCV002373074, ESM-1b 1.00, AlphaMissense 1.00, Uncertain significance, Hereditary cancer-predisposing syndrome
- A31G (p.Ala31Gly), rs730882127, ClinGen CA013158, ClinVar RCV000161932, ClinVar RCV001149363, REVEL 0.91, ESM-1b 1.00, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Colorectal cancer, hereditary nonp
Public MLH1 analysis runs
- MLH1 analysis run — MLH1 (3,606 variants) — completed 2026-05-15