POLE (Q07864) variants and mutations
POLE (also known as Q07864) is a human protein-coding gene encoding a DNA polymerase epsilon catalytic subunit A protein. It performs leading-strand DNA synthesis and proofreads newly incorporated bases during replication. Germline exonuclease-domain variants cause polymerase-proofreading-associated polyposis, while somatic proofreading defects create ultramutated tumors with distinctive mutation signatures. This analysis covers 8,115 POLE variants and mutations. Of these, 59% have computational variant effect predictions. Disease context includes colorectal cancer, susceptibility to, 12, intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia conge, and Facial dysmorphism - immunodeficiency - livedo - short stature. Example POLE variants include M1I, M1K, and M1L.
Variant analysis overview
- Gene: POLE
- Protein: Q07864
- UniProt accession: Q07864
- Organism: Homo sapiens
- Variants analyzed: 8115
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 7,962 unspecified-consequence records; 1 stop retained variant; 13 frameshift variants; 39 missense variants; 81 synonymous variants; 5 stop-gained variants; 3 splice-region variants; 6 in-frame deletions; 1 in-frame insertions; 4 substitution
- Prediction scores: 4,789 variants have prediction scores (59% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: colorectal cancer, susceptibility to, 12, intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia conge, Facial dysmorphism - immunodeficiency - livedo - short stature, facial dysmorphism-immunodeficiency-livedo-short stature syndrome, non-small cell lung carcinoma, B-cell chronic lymphocytic leukemia, acute myeloid leukemia, exocrine pancreatic carcinoma, acute lymphoblastic leukemia, colorectal cancer, neoplasm, breast carcinoma.
Protein structure and variant hotspots
- Protein features: 8 binding sites; 4 post-translational modification sites.
- PTM context: 14 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, MaveDB, LitVar.
Notable POLE variants
Examples include M1I, M1K, M1L, M1R, M1T, M1V, S2C, S2F. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs1555231433, ClinGen CA387373579, ClinVar RCV002358872, ClinVar RCV003540036, MetaLR 0.01, MetaSVM -0.99, Pathogenic
- M1K (p.Met1Lys), rs879254126, ClinGen CA387373585, ClinVar RCV000578827, ClinVar RCV001535559, MetaLR 0.01, MetaSVM -0.99, Uncertain significance
- M1L (p.Met1Leu), rs878854847, ClinGen CA10583037, ClinVar RCV000231516, ClinVar RCV000235594, MetaLR 0.01, MetaSVM -0.96, Pathogenic
- M1R (p.Met1Arg), rs879254126, ClinGen CA16042135, ClinVar RCV000411050, ClinVar RCV003541033, MetaLR 0.01, MetaSVM -0.99, Pathogenic
- M1T (p.Met1Thr), rs879254126, ClinGen CA10584417, ClinVar RCV000235663, ClinVar RCV000563606, MetaLR 0.01, MetaSVM -0.99, Uncertain significance
- M1V (p.Met1Val), rs878854847, ClinGen CA16613761, ClinVar RCV000462229, ClinVar RCV000573016, MetaLR 0.01, MetaSVM -0.96, Uncertain significance
- S2C (p.Ser2Cys), rs1060500890, ClinGen CA387373562, ClinVar RCV002356942, ClinVar RCV003541295, REVEL 0.02, CADD 13.30, Likely benign
- S2F (p.Ser2Phe), rs1060500890, ClinGen CA16613680, ClinVar RCV001753874, ClinVar RCV005260111, REVEL 0.04, CADD 17.40, Likely benign
- L3P (p.Leu3Pro), rs2542222434, ClinGen CA387373552, ClinVar RCV003319538, REVEL 0.11, CADD 23.10, Uncertain significance, not provided
- L3V (p.Leu3Val), rs1018143132, ClinGen CA246308283, ClinVar RCV000550377, ClinVar RCV003655117, REVEL 0.04, CADD 15.50, Likely benign
- R4G (p.Arg4Gly), rs1010746038, ClinGen CA246308278, ClinVar RCV003539919, ClinVar RCV005463020, REVEL 0.02, CADD 21.60, Likely benign
- R4K (p.Arg4Lys), rs2542222395, ClinGen CA387373540, ClinVar RCV003658125, Uncertain significance, not provided
- S5C (p.Ser5Cys), rs2043299375, ClinGen CA387373528, ClinVar RCV003771105, Ensembl rs2043299375, AlphaMissense 0.06, MetaLR 0.00, Uncertain significance
- S5G (p.Ser5Gly), rs2043299375, ClinGen CA387373525, ClinVar RCV003656526, ClinVar RCV004776303, REVEL 0.04, AlphaMissense 0.06, Uncertain significance
- S5N (p.Ser5Asn), rs1167872104, ClinGen CA387373521, ClinVar RCV003541111, ClinVar RCV005262190, REVEL 0.02, CADD 1.08, Likely benign
- S5R (p.Ser5Arg), rs1361332747, ClinGen CA387373514, ClinVar RCV003540762, TOPMed rs1361332747, REVEL 0.01, CADD 17.40, Conflicting interpretations, not provided; Hereditary cancer-predisposing syndrome
- G6A (p.Gly6Ala), rs772972882, ClinGen CA387373500, ClinVar RCV004524050, AlphaMissense 0.11, MetaLR 0.01, Uncertain significance, Hereditary cancer-predisposing syndrome
- G6C (p.Gly6Cys), rs202220778, ClinGen CA387373505, ClinVar RCV003656935, 1000Genomes rs202220778, REVEL 0.02, CADD 16.00, Benign
- G6D (p.Gly6Asp), rs772972882, ClinGen CA6894472, ClinVar RCV001548150, ClinVar RCV005260097, REVEL 0.02, AlphaMissense 0.11, Likely benign
- G6R (p.Gly6Arg), rs202220778, ClinGen CA248991, cosmic curated COSV57686, ClinVar RCV000202795, REVEL 0.03, CADD 9.13, Benign
- G6S (p.Gly6Ser), rs202220778, ClinGen CA387373509, ClinVar RCV002466639, ClinVar RCV005262310, REVEL 0.05, CADD 4.33, Benign
- G6V (p.Gly6Val), rs772972882, ClinGen CA387373498, ClinVar RCV003657559, ExAC rs772972882, REVEL 0.01, AlphaMissense 0.11, Uncertain significance, not provided
- G7E (p.Gly7Glu), rs929537284, ClinGen CA246308267, ClinVar RCV003656677, ClinVar RCV004545139, REVEL 0.04, CADD 15.50, Likely benign
- G7R (p.Gly7Arg), rs771930571, ClinGen CA6894471, ClinVar RCV002422829, ClinVar RCV003539328, REVEL 0.09, CADD 15.70, Likely benign
- G7W (p.Gly7Trp), rs771930571, ClinGen CA387373489, ClinVar RCV003776738, REVEL 0.09, CADD 16.90, Uncertain significance, not provided
- R8G (p.Arg8Gly), rs1196946399, ClinGen CA387373480, ClinVar RCV003540922, ClinVar RCV005260403, REVEL 0.10, CADD 22.80, Uncertain significance
- R8P (p.Arg8Pro), rs2136052243, ClinGen CA387373472, ClinVar RCV003168085, ClinVar RCV005101002, REVEL 0.13, CADD 21.90, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome
- R8Q (p.Arg8Gln), rs2136052243, ClinGen CA387373474, ClinVar RCV003541374, ClinVar RCV005262432, REVEL 0.09, CADD 20.80, Uncertain significance
- R8W (p.Arg8Trp), rs1196946399, ClinGen CA387373477, ClinVar RCV002442488, ClinVar RCV003655197, REVEL 0.12, CADD 22.60, Uncertain significance
- R9G (p.Arg9Gly), gnomAD rs1480510431, Uncertain significance, Hereditary cancer-predisposing syndrome
- R9Q (p.Arg9Gln), rs2043298739, ClinGen CA387373463, ClinVar RCV003160459, ClinVar RCV003656330, REVEL 0.01, CADD 13.40, Uncertain significance
- R9W (p.Arg9Trp), rs1480510431, ClinGen CA387373466, ClinVar RCV002431693, ClinVar RCV003654972, REVEL 0.03, CADD 9.91, Uncertain significance
- R10C (p.Arg10Cys), rs1245695191, ClinGen CA387373449, ClinVar RCV000679618, ClinVar RCV004026157, REVEL 0.01, CADD 19.10, Uncertain significance
- R10G (p.Arg10Gly), rs1245695191, ClinGen CA387373454, ClinVar RCV003772600, TOPMed rs1245695191, REVEL 0.02, CADD 15.30, Uncertain significance
- R10H (p.Arg10His), Ensembl rs2136052183, REVEL 0.08, CADD 9.79, Uncertain significance, not provided
- A11G (p.Ala11Gly), rs1060500821, ClinGen CA387373430, ClinVar RCV001762585, ClinVar RCV005262417, REVEL 0.02, CADD 9.04, Likely benign
- A11P (p.Ala11Pro), rs1593099072, ClinGen CA387373437, ClinVar RCV003656809, ClinVar RCV004036265, REVEL 0.03, CADD 10.10, Uncertain significance
- A11S (p.Ala11Ser), rs1593099072, ClinGen CA387373435, ClinVar RCV003772478, TOPMed rs1593099072, REVEL 0.01, CADD 5.82, Uncertain significance
- A11T (p.Ala11Thr), rs1593099072, ClinGen CA387373439, ClinVar RCV002325569, ClinVar RCV003540966, REVEL 0.01, CADD 8.77, Uncertain significance
- A11V (p.Ala11Val), rs1060500821, ClinGen CA16613759, ClinVar RCV003766493, gnomAD rs1060500821, REVEL 0.01, CADD 7.81, Uncertain significance
- D12G (p.Asp12Gly), rs2136052132, ClinGen CA387373415, ClinVar RCV003658207, Ensembl rs2136052132, REVEL 0.04, CADD 16.80, Uncertain significance, not provided
- D12N (p.Asp12Asn), rs1355767159, ClinGen CA387373426, ClinVar RCV001557430, ClinVar RCV002477449, REVEL 0.06, CADD 15.60, Likely benign
- P13A (p.Pro13Ala), rs747831153, ClinGen CA387373405, ClinVar RCV003656352, ExAC rs747831153, AlphaMissense 0.05, MetaLR 0.01, Uncertain significance
- P13L (p.Pro13Leu), rs878854865, ClinGen CA10583036, ClinVar RCV003133194, ClinVar RCV006424604, REVEL 0.05, AlphaMissense 0.07, Likely benign
- P13Q (p.Pro13Gln), rs878854865, ClinGen CA387373400, ClinVar RCV003770751, Ensembl rs878854865, REVEL 0.03, AlphaMissense 0.07, Uncertain significance
- P13R (p.Pro13Arg), rs878854865, ClinGen CA387373398, ClinVar RCV003735672, Ensembl rs878854865, AlphaMissense 0.07, MetaLR 0.01, Uncertain significance, not provided
- P13S (p.Pro13Ser), rs747831153, ClinGen CA6894470, ClinVar RCV003656545, ClinVar RCV005463297, REVEL 0.02, AlphaMissense 0.05, Likely benign
- G14A (p.Gly14Ala), rs1052196814, ClinGen CA387373385, ClinVar RCV003658841, ClinVar RCV005264357, REVEL 0.04, CADD 5.27, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- G14D (p.Gly14Asp), rs1052196814, ClinGen CA246308259, ClinVar RCV002327533, ClinVar RCV003656603, REVEL 0.08, CADD 9.62, Uncertain significance
- G14R (p.Gly14Arg), rs2542221939, ClinGen CA2697551655, ClinVar RCV003542257, ClinVar RCV005714977, Pathogenic
- G14S (p.Gly14Ser), rs2136052104, ClinGen CA387373394, ClinVar RCV003657622, Ensembl rs2136052104, REVEL 0.02, CADD 6.65, Uncertain significance, not provided
- G14V (p.Gly14Val), rs1052196814, ClinGen CA387373382, ClinVar RCV001770821, ClinVar RCV002329729, REVEL 0.04, CADD 11.80, Uncertain significance
- A15P (p.Ala15Pro), rs1060500788, ClinGen CA387373378, ClinVar RCV001356646, ClinVar RCV002332621, AlphaMissense 0.07, MetaLR 0.01, Likely benign
- A15T (p.Ala15Thr), rs1060500788, ClinGen CA16613754, ClinVar RCV001563277, ClinVar RCV005260063, REVEL 0.04, AlphaMissense 0.07, Likely benign
- A15V (p.Ala15Val), rs1565986587, ClinGen CA387373372, ClinVar RCV003321715, ClinVar RCV003540648, REVEL 0.02, CADD 9.64, Uncertain significance
- D16A (p.Asp16Ala), rs1333842547, ClinGen CA387373362, ClinVar RCV003294095, ClinVar RCV003656091, REVEL 0.03, CADD 19.90, Uncertain significance
- D16E (p.Asp16Glu), TOPMed rs1057523833, gnomAD rs1057523833, Uncertain significance, Hereditary cancer-predisposing syndrome
- D16G (p.Asp16Gly), rs1333842547, ClinGen CA387373361, ClinVar RCV003540906, ClinVar RCV005260396, REVEL 0.05, CADD 22.40, Uncertain significance
- D16H (p.Asp16His), rs1241114520, ClinGen CA387373364, ClinVar RCV003540545, ClinVar RCV004944069, REVEL 0.04, CADD 22.40, Uncertain significance
- D16N (p.Asp16Asn), rs1241114520, ClinGen CA387373365, ClinVar RCV003540014, gnomAD rs1241114520, REVEL 0.05, CADD 17.40, Uncertain significance
- D16V (p.Asp16Val), rs1333842547, ClinGen CA387373359, ClinVar RCV002334496, ClinVar RCV003655233, REVEL 0.06, CADD 21.60, Uncertain significance
- G17A (p.Gly17Ala), rs2043297640, ClinGen CA387373338, ClinVar RCV003656861, Ensembl rs2043297640, AlphaMissense 0.07, MetaLR 0.01, Uncertain significance
- G17C (p.Gly17Cys), rs1243827536, ClinGen CA387373344, ClinVar RCV003577322, TOPMed rs1243827536, REVEL 0.04, CADD 16.50, Uncertain significance, not provided
- G17S (p.Gly17Ser), rs1243827536, ClinGen CA387373349, ClinVar RCV003303070, ClinVar RCV003540494, REVEL 0.04, CADD 14.00, Uncertain significance
- E18* (p.Glu18Ter), rs1555231403, ClinGen CA387373329, cosmic curated COSV10962, ClinVar RCV002343364, AlphaMissense 0.15, MetaLR 0.01, Pathogenic
- E18D (p.Glu18Asp), rs1311350422, ClinGen CA387373321, ClinVar RCV003767073, ClinVar RCV004944005, REVEL 0.04, CADD 6.48, Uncertain significance
- E18G (p.Glu18Gly), Ensembl rs2136051922, REVEL 0.01, CADD 21.00
- E18K (p.Glu18Lys), rs1555231403, ClinGen CA387373333, cosmic curated COSV57675, ClinVar RCV003656361, REVEL 0.03, AlphaMissense 0.15, Pathogenic
- E18Q (p.Glu18Gln), rs1555231403, ClinGen CA387373331, ClinVar RCV003540942, Ensembl rs1555231403, AlphaMissense 0.15, MetaLR 0.01, Pathogenic
- A19G (p.Ala19Gly), gnomAD rs1395688602, Uncertain significance, Hereditary cancer-predisposing syndrome
- A19T (p.Ala19Thr), rs1391962080, ClinGen CA387373317, ClinVar RCV002350598, ClinVar RCV003770757, REVEL 0.04, CADD 9.24, Uncertain significance
- A19V (p.Ala19Val), rs1395688602, ClinGen CA387373308, ClinVar RCV003656391, ClinVar RCV005463252, REVEL 0.02, CADD 14.30, Uncertain significance
- S20G (p.Ser20Gly), rs1405389237, ClinGen CA387373299, ClinVar RCV003539357, TOPMed rs1405389237, REVEL 0.01, CADD 10.20, Uncertain significance
- S20R (p.Ser20Arg), rs1405389237, ClinGen CA387373301, cosmic curated COSV10026, ClinVar RCV002352392, REVEL 0.01, CADD 14.10, Uncertain significance, Hereditary cancer-predisposing syndrome; Colorectal cancer, susceptibility to, 1
- S20T (p.Ser20Thr), gnomAD rs2043297204, REVEL 0.02, CADD 7.85
- R21K (p.Arg21Lys), rs1365779443, ClinGen CA387373273, ClinVar RCV003541150, TOPMed rs1365779443, REVEL 0.05, CADD 24.00, Uncertain significance
- R21M (p.Arg21Met), TOPMed rs1365779443, gnomAD rs1365779443, REVEL 0.07, CADD 27.60, Uncertain significance, not provided
- R21S (p.Arg21Ser), rs2136035034, ClinGen CA387370740, cosmic curated COSV57673, ClinVar RCV003670861, AlphaMissense 0.17, MetaLR 0.01, Uncertain significance, not provided
- D22E (p.Asp22Glu), Ensembl rs2136034990, Uncertain significance, not provided
- D22G (p.Asp22Gly), cosmic curated COSV57693, Ensembl rs1060500864, Uncertain significance, not provided
- D22H (p.Asp22His), Ensembl rs2136035020
- D22N (p.Asp22Asn), Ensembl rs2136035020, Uncertain significance, Hereditary cancer-predisposing syndrome; Polymerase proofreading-related adenoma
- D22V (p.Asp22Val), rs1060500864, ClinGen CA16614069, ClinVar RCV003766520, ClinVar RCV004943863, REVEL 0.24, CADD 23.20, Uncertain significance
- D22Y (p.Asp22Tyr), Ensembl rs2136035020, Uncertain significance, Hereditary cancer-predisposing syndrome
- D23E (p.Asp23Glu), Ensembl rs2136034949
- D23G (p.Asp23Gly), rs765898876, ClinGen CA6894455, ClinVar RCV000763825, ClinVar RCV001534278, REVEL 0.25, AlphaMissense 0.15, Uncertain significance
- D23H (p.Asp23His), rs970095477, ClinGen CA387370710, NCI-TCGA Cosmic COSV5767, cosmic curated COSV57674, REVEL 0.26, CADD 24.10, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- D23N (p.Asp23Asn), TOPMed rs970095477, gnomAD rs970095477, REVEL 0.12, CADD 22.20, Uncertain significance
- D23V (p.Asp23Val), rs765898876, ClinGen CA387370704, ClinVar RCV003658825, ClinVar RCV004942971, AlphaMissense 0.15, MetaLR 0.02, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- D23Y (p.Asp23Tyr), rs970095477, ClinGen CA387370708, ClinVar RCV003160539, ClinVar RCV003541136, REVEL 0.32, CADD 23.10, Uncertain significance
- G24C (p.Gly24Cys), Ensembl rs2136034939, Uncertain significance
- G24D (p.Gly24Asp), rs2043162480, ClinGen CA387370671, ClinVar RCV003656434, ClinVar RCV004030788, REVEL 0.14, CADD 17.20, Uncertain significance
- G24R (p.Gly24Arg), cosmic curated COSV57687, Ensembl rs2136034939, Uncertain significance
- G24S (p.Gly24Ser), rs2136034939, ClinGen CA387370695, cosmic curated COSV57686, ClinVar RCV003658847, AlphaMissense 0.14, MetaLR 0.03, Uncertain significance, not provided
- A25D (p.Ala25Asp), rs561834381, ClinGen CA6894452, ClinVar RCV003656592, ClinVar RCV004944900, REVEL 0.06, AlphaMissense 0.07, Uncertain significance
- A25G (p.Ala25Gly), ExAC rs561834381, TOPMed rs561834381, gnomAD rs561834381, Uncertain significance
- A25P (p.Ala25Pro), ExAC rs773204331, TOPMed rs773204331, gnomAD rs773204331, Uncertain significance
- A25S (p.Ala25Ser), rs773204331, ClinGen CA387370661, cosmic curated COSV10588, NCI-TCGA Cosmic COSV5768, REVEL 0.03, CADD 0.01, Uncertain significance
- A25T (p.Ala25Thr), rs773204331, ClinGen CA6894453, NCI-TCGA Cosmic COSV5768, cosmic curated COSV57689, REVEL 0.03, CADD 0.06, Likely benign
- A25V (p.Ala25Val), rs561834381, ClinGen CA387370652, ClinVar RCV003302879, ClinVar RCV003655114, AlphaMissense 0.07, MetaLR 0.01, Uncertain significance
- T26A (p.Thr26Ala), rs182282150, ClinGen CA6894451, cosmic curated COSV57681, ClinVar RCV002461972, REVEL 0.07, AlphaMissense 0.06, Likely benign
- T26I (p.Thr26Ile), rs2043162143, ClinGen CA387370636, ClinVar RCV002411753, ClinVar RCV003313190, REVEL 0.07, AlphaMissense 0.06, Uncertain significance
- T26N (p.Thr26Asn), rs2043162143, ClinGen CA387370637, ClinVar RCV003656369, TOPMed rs2043162143, AlphaMissense 0.06, MetaLR 0.00, Uncertain significance
- T26P (p.Thr26Pro), 1000Genomes rs182282150, ExAC rs182282150, TOPMed rs182282150, gnomAD rs182282150, Likely benign
- T26S (p.Thr26Ser), rs182282150, ClinGen CA387370643, ClinVar RCV003773411, 1000Genomes rs182282150, AlphaMissense 0.06, MetaLR 0.01, Uncertain significance, not provided
- S27C (p.Ser27Cys), Ensembl rs1593088347, Likely benign
- S27F (p.Ser27Phe), rs1593088347, ClinGen CA387370618, ClinVar RCV001759512, ClinVar RCV004027597, REVEL 0.12, CADD 23.20, Likely benign
- S27P (p.Ser27Pro), rs2136034847, ClinGen CA387370630, ClinVar RCV003296941, ClinVar RCV003542480, AlphaMissense 0.07, MetaLR 0.01, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- S27T (p.Ser27Thr), Ensembl rs2136034847, Uncertain significance
- S28* (p.Ser28Ter), Ensembl rs2136034810
- S28L (p.Ser28Leu), Ensembl rs2136034810
- S28P (p.Ser28Pro), Ensembl rs2136034823
- S28T (p.Ser28Thr), Ensembl rs2136034823
- V29D (p.Val29Asp), rs2136034786, ClinGen CA387370581, ClinVar RCV002466218, ClinVar RCV003679137, REVEL 0.13, CADD 1.93, Uncertain significance, not provided; not specified
- V29G (p.Val29Gly), Ensembl rs2136034786, Uncertain significance
- V29L (p.Val29Leu), Ensembl rs2136034796
- S30* (p.Ser30Ter), rs997586826, ClinGen CA387370560, ClinVar RCV003541519, ClinVar RCV006424857, CADD 40.00, Pathogenic
- S30A (p.Ser30Ala), rs2136034778, ClinGen CA387370565, ClinVar RCV003658639, AlphaMissense 0.10, MetaLR 0.01, Uncertain significance, not provided
- S30L (p.Ser30Leu), rs997586826, ClinGen CA246303564, cosmic curated COSV57675, ClinVar RCV003539954, REVEL 0.20, CADD 23.30, Pathogenic
- S30T (p.Ser30Thr), Ensembl rs2136034778
- S30W (p.Ser30Trp), TOPMed rs997586826, gnomAD rs997586826, Pathogenic
- A31P (p.Ala31Pro), 1000Genomes rs34047482, ESP rs34047482, ExAC rs34047482, TOPMed rs34047482, Benign
- A31S (p.Ala31Ser), rs34047482, ClinGen CA349719, ClinVar RCV000205587, ClinVar RCV000433484, REVEL 0.20, CADD 15.20, Benign
- A31T (p.Ala31Thr), 1000Genomes rs34047482, ESP rs34047482, ExAC rs34047482, TOPMed rs34047482, REVEL 0.22, CADD 17.10, Benign
- A31V (p.Ala31Val), rs2043161643, ClinGen CA387370535, ClinVar RCV003549464, ClinVar RCV005467977, REVEL 0.16, CADD 14.30, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome
- L32F (p.Leu32Phe), rs781513537, ClinGen CA6894448, ClinVar RCV001281043, ClinVar RCV003165639, REVEL 0.08, CADD 10.60, Likely benign
- L32H (p.Leu32His), Ensembl rs878854900, Uncertain significance
- L32P (p.Leu32Pro), rs878854900, ClinGen CA387370512, ClinVar RCV005091279, ClinVar RCV005260230, REVEL 0.17, CADD 22.30, Uncertain significance
- L32R (p.Leu32Arg), rs878854900, ClinGen CA10583033, cosmic curated COSV57693, ClinVar RCV002374369, REVEL 0.21, CADD 20.50, Uncertain significance
- L32V (p.Leu32Val), rs781513537, ClinGen CA387370526, cosmic curated COSV10885, ClinVar RCV003658064, REVEL 0.05, CADD 9.47, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- K33* (p.Lys33Ter), Ensembl rs2136034673, Uncertain significance
- K33E (p.Lys33Glu), rs2136034673, ClinGen CA387370500, ClinVar RCV003772465, Ensembl rs2136034673, AlphaMissense 0.37, MetaLR 0.01, Uncertain significance
- K33M (p.Lys33Met), gnomAD rs2043161391, Uncertain significance
- K33N (p.Lys33Asn), TOPMed rs1270401168, gnomAD rs1270401168, REVEL 0.17, CADD 18.30, Likely benign
- K33R (p.Lys33Arg), rs2043161391, ClinGen CA387370486, ClinVar RCV003773013, ClinVar RCV004044596, REVEL 0.16, AlphaMissense 0.36, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- K33T (p.Lys33Thr), rs2043161391, ClinGen CA387370490, ClinVar RCV002387438, gnomAD rs2043161391, AlphaMissense 0.36, MetaLR 0.01, Uncertain significance, Hereditary cancer-predisposing syndrome
- R34C (p.Arg34Cys), rs771051323, ClinGen CA6894447, NCI-TCGA Cosmic COSV5768, cosmic curated COSV57682, REVEL 0.32, CADD 29.20, Uncertain significance
- R34G (p.Arg34Gly), ExAC rs771051323, TOPMed rs771051323, gnomAD rs771051323, Uncertain significance, Hereditary cancer-predisposing syndrome
- R34H (p.Arg34His), rs747005851, ClinGen CA6894446, ClinVar RCV003656838, ClinVar RCV005271138, REVEL 0.41, CADD 26.40, Uncertain significance
- R34L (p.Arg34Leu), rs747005851, ClinGen CA16613676, NCI-TCGA Cosmic COSV5767, cosmic curated COSV57673, REVEL 0.41, CADD 23.80, Uncertain significance
- R34P (p.Arg34Pro), ExAC rs747005851, TOPMed rs747005851, gnomAD rs747005851, Uncertain significance
- R34S (p.Arg34Ser), ExAC rs771051323, TOPMed rs771051323, gnomAD rs771051323, REVEL 0.29, CADD 23.80, Uncertain significance
- L35M (p.Leu35Met), NCI-TCGA Cosmic COSV5768, cosmic curated COSV57689, Variant assessed as somatic; moderate impact.
- L35Q (p.Leu35Gln), rs2043161231, ClinGen CA387370432, ClinVar RCV002268419, ClinVar RCV003541126, REVEL 0.41, CADD 26.50, Uncertain significance
- L35V (p.Leu35Val), Ensembl rs2136034598, Likely benign
- E36* (p.Glu36Ter), cosmic curated COSV57676, ESP rs370268888, ExAC rs370268888, TOPMed rs370268888, AlphaMissense 0.12, MetaLR 0.01, Uncertain significance
- E36D (p.Glu36Asp), Ensembl rs1054727206
- E36K (p.Glu36Lys), rs370268888, ClinGen CA387370413, ClinVar RCV003657991, AlphaMissense 0.12, MetaLR 0.01, Uncertain significance, not provided
- E36N (p.Glu36Asn), rs2542198020, ClinGen CA2580086131, ClinVar RCV003658618, Pathogenic
- E36Q (p.Glu36Gln), rs370268888, ClinGen CA6894444, ClinVar RCV003228972, ClinVar RCV005260283, REVEL 0.23, AlphaMissense 0.12, Uncertain significance
- E36V (p.Glu36Val), rs2542197998, ClinGen CA387370392, ClinVar RCV003658519, Uncertain significance, not provided
- R37G (p.Arg37Gly), ExAC rs753101641, TOPMed rs753101641, gnomAD rs753101641, Uncertain significance
- R37L (p.Arg37Leu), cosmic curated COSV57692, ESP rs377002290, ExAC rs377002290, TOPMed rs377002290, Uncertain significance
- R37P (p.Arg37Pro), ESP rs377002290, ExAC rs377002290, TOPMed rs377002290, gnomAD rs377002290, Pathogenic, Autosomal dominant nonsyndromic hearing loss 41
- R37Q (p.Arg37Gln), rs377002290, ClinGen CA6894442, ClinVar RCV001585629, ClinVar RCV005268716, REVEL 0.28, CADD 22.30, Uncertain significance
- R37W (p.Arg37Trp), rs753101641, ClinGen CA6894443, cosmic curated COSV10026, ClinVar RCV000650792, REVEL 0.35, CADD 24.00, Uncertain significance
- S38C (p.Ser38Cys), rs879254247, ClinGen CA10584416, ClinVar RCV000236959, ClinVar RCV005462926, REVEL 0.12, CADD 22.40, Likely benign
- S38N (p.Ser38Asn), rs141424313, ClinGen CA6894441, ClinVar RCV001584137, ClinVar RCV004022579, REVEL 0.07, CADD 19.80, Likely benign
- S38R (p.Ser38Arg), rs2043160789, TOPMed rs2043160789, ClinGen CA387370336, cosmic curated COSV10588, REVEL 0.16, CADD 14.30, Uncertain significance
- S38T (p.Ser38Thr), 1000Genomes rs141424313, ESP rs141424313, ExAC rs141424313, TOPMed rs141424313, Likely benign
- Q39* (p.Gln39Ter), Ensembl rs2136034450, AlphaMissense 0.10, MetaLR 0.01, Uncertain significance
- Q39E (p.Gln39Glu), rs2136034450, ClinGen CA387370323, ClinVar RCV003675092, Ensembl rs2136034450, AlphaMissense 0.10, MetaLR 0.01, Uncertain significance, not provided
- Q39H (p.Gln39His), Ensembl rs2136034434
- Q39K (p.Gln39Lys), Ensembl rs2136034450, Uncertain significance
- Q39L (p.Gln39Leu), gnomAD rs1467498021, Uncertain significance
- Q39R (p.Gln39Arg), rs1467498021, ClinGen CA387370304, ClinVar RCV003156413, ClinVar RCV005467936, REVEL 0.24, CADD 20.30, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- W40* (p.Trp40Ter), Ensembl rs2136034390, CADD 37.00, Pathogenic
- W40C (p.Trp40Cys), Ensembl rs2136034390
- W40G (p.Trp40Gly), Ensembl rs2136034425
- W40L (p.Trp40Leu), Ensembl rs1565981653, Pathogenic
- W40R (p.Trp40Arg), Ensembl rs2136034425
- W40S (p.Trp40Ser), Ensembl rs1565981653, Pathogenic
- T41K (p.Thr41Lys), rs148269473, ClinGen CA387370230, ClinVar RCV003657616, 1000Genomes rs148269473, AlphaMissense 0.23, MetaLR 0.01, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- T41M (p.Thr41Met), rs148269473, ClinGen CA6894440, ClinVar RCV001544558, ClinVar RCV004539937, REVEL 0.18, AlphaMissense 0.23, Uncertain significance
- T41R (p.Thr41Arg), rs148269473, ClinGen CA387370227, ClinVar RCV003541130, ClinVar RCV005712346, AlphaMissense 0.23, MetaLR 0.01, Uncertain significance
- D42A (p.Asp42Ala), rs749886101, ClinGen CA6894437, ClinVar RCV003540638, ExAC rs749886101, REVEL 0.49, CADD 26.70, Uncertain significance
- D42E (p.Asp42Glu), Ensembl rs2136034323, REVEL 0.19, CADD 16.20
- D42G (p.Asp42Gly), ExAC rs749886101, gnomAD rs749886101, Uncertain significance, Hereditary cancer-predisposing syndrome
- D42H (p.Asp42His), Ensembl rs2136034354, Uncertain significance
- D42N (p.Asp42Asn), rs2136034354, ClinGen CA387370213, NCI-TCGA Cosmic COSV5768, cosmic curated COSV57684, AlphaMissense 0.69, MetaLR 0.08, Uncertain significance, Hereditary cancer-predisposing syndrome
Public POLE analysis runs
- POLE analysis run — POLE (8,115 variants) — completed 2026-08-18