POLD1 (P28340) variants and mutations
POLD1 (also known as P28340) is a human protein-coding gene encoding a DNA polymerase delta catalytic subunit protein. It performs much of lagging-strand DNA synthesis and proofreads newly replicated DNA through its exonuclease activity. Germline proofreading-domain variants cause polymerase-proofreading-associated polyposis and cancer predisposition, while other variants can produce developmental progeroid syndromes. This analysis covers 3,864 POLD1 variants and mutations. Of these, 66% have computational variant effect predictions. Disease context includes mandibular hypoplasia-deafness-progeroid syndrome, non-small cell lung carcinoma, and acute lymphoblastic leukemia. Example POLD1 variants include M1K, M1L, and M1T.
Variant analysis overview
- Gene: POLD1
- Protein: P28340
- UniProt accession: P28340
- Organism: Homo sapiens
- Variants analyzed: 3864
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 3,637 unspecified-consequence records; 79 missense variants; 105 synonymous variants; 12 frameshift variants; 1 protein altering variant; 9 in-frame deletions; 2 in-frame insertions; 10 stop-gained variants; 6 splice-region variants; 2 substitution
- Prediction scores: 2,554 variants have prediction scores (66% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: mandibular hypoplasia-deafness-progeroid syndrome, non-small cell lung carcinoma, acute lymphoblastic leukemia, colorectal cancer, acute myeloid leukemia, B-cell chronic lymphocytic leukemia, colorectal cancer, susceptibility to, 10, exocrine pancreatic carcinoma, breast carcinoma, neoplasm, breast cancer, ovarian carcinoma.
Protein structure and variant hotspots
- Protein features: 8 binding sites; 1 post-translational modification sites.
- PTM context: 6 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 POLD1 variants
Examples include M1K, M1L, M1T, M1V, D2E, D2G, D2H, D2Y. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1K (p.Met1Lys), rs1057517594, ClinGen CA16042185, ClinVar RCV000411507, ClinVar RCV000570492, MetaLR 0.22, MetaSVM -0.64, Uncertain significance, Hereditary cancer-predisposing syndrome; Colorectal cancer, susceptibility to, 1
- M1L (p.Met1Leu), rs2038467552, ClinGen CA406969949, ClinVar RCV001961511, MetaLR 0.27, MetaSVM -0.56, Uncertain significance, Colorectal cancer, susceptibility to, 10
- M1T (p.Met1Thr), rs1057517594, ClinGen CA406969952, ClinVar RCV001017954, ClinVar RCV001302452, MetaLR 0.22, MetaSVM -0.64, Uncertain significance, not provided; Colorectal cancer, susceptibility to, 10; POLD1-related disorder
- M1V (p.Met1Val), rs2038467552, ClinGen CA406969950, ClinVar RCV001048613, MetaLR 0.27, MetaSVM -0.56, Uncertain significance, Colorectal cancer, susceptibility to, 10
- D2E (p.Asp2Glu), Ensembl rs2122193488
- D2G (p.Asp2Gly), rs2122193463, ClinGen CA406969961, ClinVar RCV002357963, ClinVar RCV006559084, AlphaMissense 0.15, MetaLR 0.06, Uncertain significance, Hereditary cancer-predisposing syndrome; Colorectal cancer, susceptibility to, 1
- D2H (p.Asp2His), rs2038467819, ClinGen CA406969958, ClinVar RCV001343532, ClinVar RCV003238350, AlphaMissense 0.37, MetaLR 0.07, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Colorectal cancer, suscep
- D2Y (p.Asp2Tyr), rs2038467819, ClinGen CA406969959, ClinVar RCV002851677, REVEL 0.08, AlphaMissense 0.37, Uncertain significance, Colorectal cancer, susceptibility to, 10
- G3D (p.Gly3Asp), rs2038467920, ClinGen CA406969968, ClinVar RCV001070117, Ensembl rs2038467920, REVEL 0.10, CADD 22.90, Uncertain significance, Colorectal cancer, susceptibility to, 10
- G3V (p.Gly3Val), NCI-TCGA Cosmic COSV1014, cosmic curated COSV10148, REVEL 0.05, CADD 22.80, Variant assessed as somatic; moderate impact.
- G3S (p.Gly3Ser), gnomAD 19-50398858-G-A, REVEL 0.04, CADD 16.30
- G3G (p.Gly3Gly), rs1060501826, gnomAD 19-50398860-C-T, CADD 10.90
- K4E (p.Lys4Glu), rs2038468125, ClinGen CA406969972, ClinVar RCV003640406, AlphaMissense 0.30, MetaLR 0.11, Uncertain significance, Colorectal cancer, susceptibility to, 10
- K4Q (p.Lys4Gln), rs2038468125, ClinGen CA406969971, ClinVar RCV001052280, ClinVar RCV005702396, AlphaMissense 0.30, MetaLR 0.11, Uncertain significance, Colorectal cancer, susceptibility to, 10; Hereditary cancer-predisposing syndrom
- K4T (p.Lys4Thr), rs2122193607, ClinGen CA406969974, ClinVar RCV001974218, Ensembl rs2122193607, AlphaMissense 0.54, MetaLR 0.10, Uncertain significance, Colorectal cancer, susceptibility to, 10
- R5L (p.Arg5Leu), ExAC rs748471297, TOPMed rs748471297, gnomAD rs748471297, REVEL 0.12, CADD 24.50, Likely benign
- R5Q (p.Arg5Gln), rs748471297, ClinGen CA9595581, NCI-TCGA Cosmic COSV1014, cosmic curated COSV10148, REVEL 0.09, CADD 26.60, Conflicting interpretations, Mandibular hypoplasia-deafness-progeroid syndrome; Immunodeficiency 120; Colorec
- R5W (p.Arg5Trp), rs9282830, ClinGen CA9595580, ClinVar RCV000732271, ClinVar RCV001079499, REVEL 0.25, CADD 26.30, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not specified; not provided
- R5R (p.Arg5Arg), gnomAD 19-50398864-C-A, CADD 10.70
- R6P (p.Arg6Pro), rs778275831, ClinGen CA9595584, ClinVar RCV000226679, ClinVar RCV000759220, REVEL 0.08, CADD 15.40, Conflicting interpretations, not provided; Hereditary cancer-predisposing syndrome; not specified
- R6Q (p.Arg6Gln), rs778275831, ClinGen CA9595583, ClinVar RCV000211516, ClinVar RCV000411457, REVEL 0.10, CADD 15.90, Conflicting interpretations, not specified; not provided; Colorectal cancer
- R6W (p.Arg6Trp), rs55955638, ClinGen CA9595582, cosmic curated COSV10944, ClinVar RCV000645857, REVEL 0.08, CADD 22.90, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Colorectal cancer, susceptibility to, 1
- R6L (p.Arg6Leu), gnomAD 19-50398868-G-T, REVEL 0.07, CADD 19.10
- R6R (p.Arg6Arg), rs771540531, gnomAD 19-50398869-G-A, CADD 6.94
- P7A (p.Pro7Ala), Ensembl rs2122193847, Benign
- P7Q (p.Pro7Gln), rs2038469040, ClinGen CA406969988, ClinVar RCV001043362, ClinVar RCV005463216, REVEL 0.12, CADD 9.82, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Colorectal cancer, susceptibility to, 1
- P7S (p.Pro7Ser), rs2122193847, ClinGen CA406969986, ClinVar RCV002250303, Ensembl rs2122193847, REVEL 0.14, CADD 11.70, Benign, not specified
- P7T (p.Pro7Thr), Ensembl rs2122193847, Benign
- P7P (p.Pro7Pro), rs1601188517, gnomAD 19-50398872-A-G, CADD 7.70
- G8A (p.Gly8Ala), rs2513932021, ClinGen CA406969994, ClinVar RCV002640293, Uncertain significance, Colorectal cancer, susceptibility to, 10
- G8C (p.Gly8Cys), cosmic curated COSV10593
- G8D (p.Gly8Asp), rs2513932021, ClinGen CA406969993, ClinVar RCV002583566, Uncertain significance, Colorectal cancer, susceptibility to, 10
- G8S (p.Gly8Ser), rs1187406181, ClinGen CA406969990, ClinVar RCV003641527, gnomAD rs1187406181, AlphaMissense 0.09, MetaLR 0.02, Uncertain significance, Colorectal cancer, susceptibility to, 10
- G8V (p.Gly8Val), gnomAD 19-50398874-G-T, REVEL 0.06, CADD 14.30
- G8G (p.Gly8Gly), gnomAD 19-50398875-C-A, CADD 5.64
- P9L (p.Pro9Leu), rs1555789025, ClinGen CA406970001, ClinVar RCV000645849, Ensembl rs1555789025, REVEL 0.08, CADD 16.50, Uncertain significance, Colorectal cancer, susceptibility to, 10
- P9Q (p.Pro9Gln), cosmic curated COSV10148, Ensembl rs1555789025, REVEL 0.04, CADD 15.20, Uncertain significance
- P9S (p.Pro9Ser), rs2513932031, ClinGen CA406969998, ClinVar RCV003641687, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Colorectal cancer, susceptibility to, 1
- P9T (p.Pro9Thr), gnomAD 19-50398876-C-A, REVEL 0.06, CADD 11.50
- P9R (p.Pro9Arg), gnomAD 19-50398877-C-G, REVEL 0.05, CADD 15.60
- P9P (p.Pro9Pro), rs369159202, gnomAD 19-50398878-A-G, CADD 2.46
- G10E (p.Gly10Glu), cosmic curated COSV10611, REVEL 0.06, CADD 18.70
- G10R (p.Gly10Arg), rs2038469598, ClinGen CA406970004, cosmic curated COSV70955, ClinVar RCV001248416, AlphaMissense 0.26, MetaLR 0.04, Uncertain significance, Hereditary cancer-predisposing syndrome; Colorectal cancer, susceptibility to, 1
- G10V (p.Gly10Val), cosmic curated COSV70954, REVEL 0.06, CADD 18.60, Conflicting interpretations, Colorectal cancer, susceptibility to, 10; Hereditary cancer-predisposing syndrom
- G10G (p.Gly10Gly), gnomAD 19-50398881-G-T, CADD 3.94
- P11L (p.Pro11Leu), TOPMed rs922648487, REVEL 0.05, CADD 16.40
- P11S (p.Pro11Ser), rs2122194108, ClinGen CA406970010, ClinVar RCV001990096, Ensembl rs2122194108, REVEL 0.08, CADD 2.05, Uncertain significance, Colorectal cancer, susceptibility to, 10
- P11T (p.Pro11Thr), gnomAD 19-50398882-C-A, REVEL 0.05, CADD 2.06
- P11P (p.Pro11Pro), rs3218768, gnomAD 19-50398884-C-A, CADD 0.23
- G12E (p.Gly12Glu), rs1389018181, ClinGen CA406970015, ClinVar RCV003640677, ClinVar RCV005715023, REVEL 0.05, CADD 18.70, Conflicting interpretations, Colorectal cancer, susceptibility to, 10; Hereditary cancer-predisposing syndrom
- G12R (p.Gly12Arg), rs772197667, ClinGen CA9595588, cosmic curated COSV70955, ClinVar RCV000472030, REVEL 0.09, CADD 22.10, Conflicting interpretations, Mandibular hypoplasia-deafness-progeroid syndrome; Immunodeficiency 120; Colorec
- G12W (p.Gly12Trp), gnomAD 19-50398885-G-T, REVEL 0.13, CADD 24.00
- G12V (p.Gly12Val), gnomAD 19-50398886-G-T, REVEL 0.05, CADD 22.00
- G12G (p.Gly12Gly), rs775717328, gnomAD 19-50398887-G-A, CADD 8.10
- V13E (p.Val13Glu), Ensembl rs1601188623
- V13G (p.Val13Gly), cosmic curated COSV70955, Ensembl rs1601188623, REVEL 0.03, CADD 16.20
- V13L (p.Val13Leu), rs760884573, ClinGen CA406970018, ClinVar RCV001360082, ExAC rs760884573, REVEL 0.03, CADD 12.80, Uncertain significance, Colorectal cancer, susceptibility to, 10
- V13M (p.Val13Met), rs760884573, ClinGen CA9595591, ClinVar RCV000460088, ClinVar RCV004596191, REVEL 0.02, CADD 16.30, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not specified; Colorectal cancer, susce
- V13C (p.Val13Cys), gnomAD 19-50398884-CG-C, CADD 23.50
- V13V (p.Val13Val), rs2122194344, gnomAD 19-50398890-G-A, CADD 4.03
- P14A (p.Pro14Ala), rs1402598316, ClinGen CA406970023, ClinVar RCV004516124, AlphaMissense 0.07, MetaLR 0.11, Uncertain significance, Hereditary cancer-predisposing syndrome
- P14H (p.Pro14His), rs2122194403, ClinGen CA406970027, ClinVar RCV001932296, Ensembl rs2122194403, REVEL 0.08, CADD 23.60, Uncertain significance, Colorectal cancer, susceptibility to, 10
- P14S (p.Pro14Ser), rs1402598316, ClinGen CA406970024, ClinVar RCV001363620, ClinVar RCV002322332, REVEL 0.07, AlphaMissense 0.07, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome; Colorectal cancer, suscep
- P14T (p.Pro14Thr), gnomAD 19-50398891-C-A, REVEL 0.07, CADD 21.50
- P14P (p.Pro14Pro), gnomAD 19-50398893-C-A, CADD 8.07
- P15L (p.Pro15Leu), rs1601188655, ClinGen CA406970033, ClinVar RCV000813620, Ensembl rs1601188655, AlphaMissense 0.12, MetaLR 0.05, Uncertain significance, Colorectal cancer, susceptibility to, 10
- P15S (p.Pro15Ser), rs2513932269, ClinGen CA406970030, ClinVar RCV003527083, REVEL 0.04, CADD 10.90, Conflicting interpretations, Colorectal cancer, susceptibility to, 10; Hereditary cancer-predisposing syndrom
- p.Pro15delinsLeuAla, rs2038470850, gnomAD 19-50398894-C-CTT, CADD 23.20
- P15Q (p.Pro15Gln), gnomAD 19-50398895-C-A, REVEL 0.04, CADD 18.60
- P15P (p.Pro15Pro), rs761783892, gnomAD 19-50398896-A-G, CADD 2.27
- K16E (p.Lys16Glu), rs765185645, ClinGen CA9595594, ClinVar RCV000590955, ClinVar RCV000689432, REVEL 0.06, CADD 22.80, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Colorectal cancer; not specified
- K16T (p.Lys16Thr), rs2513932328, ClinGen CA406970038, ClinVar RCV002337859, Uncertain significance, Hereditary cancer-predisposing syndrome
- K16N (p.Lys16Asn), gnomAD 19-50398899-G-T, REVEL 0.05, CADD 18.30
- R17G (p.Arg17Gly), 1000Genomes rs570461545, ExAC rs570461545, TOPMed rs570461545, gnomAD rs570461545, Likely benign
- R17L (p.Arg17Leu), rs373637566, ClinGen CA406970042, ClinVar RCV000645865, ClinVar RCV004760671, AlphaMissense 0.16, MetaLR 0.03, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided; Colorectal cancer, suscep
- R17Q (p.Arg17Gln), rs373637566, ClinGen CA9595596, ClinVar RCV000468373, ClinVar RCV001564421, REVEL 0.04, AlphaMissense 0.16, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not specified; not provided
- R17W (p.Arg17Trp), rs570461545, ClinGen CA9595595, cosmic curated COSV70954, ClinVar RCV000467060, REVEL 0.10, CADD 23.30, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided; Colorectal cancer, suscep
- R17R (p.Arg17Arg), rs570461545, gnomAD 19-50398900-C-A, CADD 7.29
- A18D (p.Ala18Asp), Ensembl rs2122194740, REVEL 0.02, CADD 14.90
- A18V (p.Ala18Val), rs2122194740, ClinGen CA406970049, ClinVar RCV003325808, ClinVar RCV004943017, REVEL 0.02, CADD 15.00, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- A18T (p.Ala18Thr), rs1568614680, ClinGen CA406970044, ClinVar RCV000701833, Ensembl rs1568614680, AlphaMissense 0.08, MetaLR 0.04, Uncertain significance, Colorectal cancer, susceptibility to, 10
- p.Ala18 Gly20del, rs1555789043, gnomAD 19-50398900-CGGGC, CADD 15.10
- A18S (p.Ala18Ser), gnomAD 19-50398903-G-T, REVEL 0.02, CADD 9.38
- A18G (p.Ala18Gly), gnomAD 19-50398904-C-G, REVEL 0.03, CADD 14.80
- R19C (p.Arg19Cys), rs368033860, ClinGen CA9595598, cosmic curated COSV10593, ClinVar RCV000473390, REVEL 0.06, CADD 21.80, Conflicting interpretations, not specified; Colorectal cancer, susceptibility to, 10; not provided
- R19H (p.Arg19His), rs3218773, ClinGen CA349025, ClinVar RCV000204841, ClinVar RCV000210816, REVEL 0.05, CADD 21.80, Benign/Likely benign, Colorectal cancer, susceptibility to, 10; Mandibular hypoplasia-deafness-progero
- R19L (p.Arg19Leu), rs3218773, ClinGen CA406970053, ClinVar RCV001043786, ClinVar RCV005712328, REVEL 0.07, CADD 21.80, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Colorectal cancer, susceptibility to, 1
- R19P (p.Arg19Pro), 1000Genomes rs3218773, ESP rs3218773, ExAC rs3218773, TOPMed rs3218773, REVEL 0.10, CADD 22.20, Benign
- R19S (p.Arg19Ser), cosmic curated COSV10148, REVEL 0.04, CADD 18.80
- R19G (p.Arg19Gly), gnomAD 19-50398906-C-G, REVEL 0.06, CADD 19.50
- G20A (p.Gly20Ala), rs778329225, ClinGen CA406970057, ClinVar RCV000810647, ClinVar RCV002352408, REVEL 0.01, AlphaMissense 0.07, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided; Colorectal cancer, suscep
- G20E (p.Gly20Glu), rs778329225, ClinGen CA9595599, ClinVar RCV000459378, ClinVar RCV001567390, REVEL 0.02, AlphaMissense 0.07, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Colorectal cancer, suscep
- G20R (p.Gly20Arg), rs1601188789, ClinGen CA406970056, ClinVar RCV000801314, ClinVar RCV005392410, REVEL 0.01, CADD 5.83, Conflicting interpretations, Colorectal cancer, susceptibility to, 10; Hereditary cancer-predisposing syndrom
- G20V (p.Gly20Val), rs778329225, ClinGen CA406970058, ClinVar RCV003050100, AlphaMissense 0.07, MetaLR 0.04, Uncertain significance, Colorectal cancer, susceptibility to, 10
- G20G (p.Gly20Gly), rs2122194932, gnomAD 19-50398911-G-A, CADD 3.91
- G21A (p.Gly21Ala), NCI-TCGA TCGA novel, REVEL 0.04, CADD 11.10, Variant assessed as somatic; high impact.
- G21C (p.Gly21Cys), rs9282831, ClinGen CA9595600, cosmic curated COSV10593, ClinVar RCV000546801, REVEL 0.09, AlphaMissense 0.09, Uncertain significance, Colorectal cancer, susceptibility to, 10; Hereditary cancer-predisposing syndrom
- G21D (p.Gly21Asp), rs771371900, ClinGen CA9595601, ClinVar RCV001317793, ClinVar RCV004034434, REVEL 0.04, CADD 12.20, Uncertain significance, Hereditary cancer-predisposing syndrome; Colorectal cancer, susceptibility to, 1
- G21R (p.Gly21Arg), rs9282831, ClinGen CA406970060, ClinVar RCV002029208, 1000Genomes rs9282831, AlphaMissense 0.09, MetaLR 0.03, Uncertain significance, Colorectal cancer, susceptibility to, 10
- G21V (p.Gly21Val), rs771371900, ClinGen CA406970062, ClinVar RCV000645848, ClinVar RCV003303048, REVEL 0.02, CADD 16.00, Uncertain significance, Colorectal cancer, susceptibility to, 10; Hereditary cancer-predisposing syndrom
- G21G (p.Gly21Gly), rs2122195020, gnomAD 19-50398914-C-T, CADD 4.50
- L22F (p.Leu22Phe), rs779418268, ClinGen CA9595602, cosmic curated COSV70954, ClinVar RCV000535041, REVEL 0.02, CADD 4.13, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Colorectal cancer, susceptibility to, 1
- L22L (p.Leu22Leu), rs745941251, gnomAD 19-50398917-C-G, CADD 1.01
- W23* (p.Trp23Ter), rs2038473555, ClinGen CA406970073, ClinVar RCV001310025, Ensembl rs2038473555, AlphaMissense 0.30, MetaLR 0.14, Uncertain significance
- W23C (p.Trp23Cys), rs2038473555, ClinGen CA406970075, ClinVar RCV002022310, ClinVar RCV004651888, REVEL 0.13, AlphaMissense 0.30, Uncertain significance, Hereditary cancer-predisposing syndrome; Colorectal cancer, susceptibility to, 1
- W23L (p.Trp23Leu), ExAC rs772263544
- W23R (p.Trp23Arg), rs1189793004, ClinGen CA406970069, ClinVar RCV001224065, ClinVar RCV002366008, REVEL 0.11, CADD 23.10, Uncertain significance, Hereditary cancer-predisposing syndrome; Colorectal cancer, susceptibility to, 1
- D24E (p.Asp24Glu), Ensembl rs2122195232, Uncertain significance, Hereditary cancer-predisposing syndrome
- D24N (p.Asp24Asn), rs1246828069, ClinGen CA406970078, cosmic curated COSV70956, ClinVar RCV001938259, REVEL 0.06, CADD 22.60, Uncertain significance, Colorectal cancer, susceptibility to, 10
- D24G (p.Asp24Gly), gnomAD 19-50398922-A-G, REVEL 0.06, CADD 23.40
- D25G (p.Asp25Gly), rs2122195283, ClinGen CA406970088, cosmic curated COSV10752, ClinVar RCV001371115, AlphaMissense 0.15, MetaLR 0.02, Uncertain significance, Hereditary cancer-predisposing syndrome; Colorectal cancer, susceptibility to, 1
- D25N (p.Asp25Asn), rs1426253750, ClinGen CA406970084, cosmic curated COSV70955, ClinVar RCV000685631, REVEL 0.07, CADD 20.90, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Colorectal cancer, susceptibility to, 1
- D25V (p.Asp25Val), rs2122195283, ClinGen CA406970089, ClinVar RCV002036734, Ensembl rs2122195283, AlphaMissense 0.15, MetaLR 0.02, Uncertain significance, Colorectal cancer, susceptibility to, 10
- D25Y (p.Asp25Tyr), gnomAD 19-50398924-G-T, REVEL 0.08, CADD 22.80
- D25E (p.Asp25Glu), rs772855121, gnomAD 19-50398925-AT-A, CADD 0.03
- D25D (p.Asp25Asp), rs1015663503, gnomAD 19-50398926-T-C, CADD 0.11
- D26G (p.Asp26Gly), rs760939854, ClinGen CA9595608, ClinVar RCV000645797, ClinVar RCV005027765, REVEL 0.13, CADD 22.60, Uncertain significance, Hereditary cancer-predisposing syndrome; Colorectal cancer, susceptibility to, 1
- D26H (p.Asp26His), ExAC rs775421347, gnomAD rs775421347, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Colorectal cancer, susceptibility to, 1
- D26N (p.Asp26Asn), cosmic curated COSV10895
- D26V (p.Asp26Val), ExAC rs760939854, gnomAD rs760939854, Uncertain significance
- D26Y (p.Asp26Tyr), gnomAD 19-50398927-G-T, REVEL 0.18, CADD 23.90
- D26D (p.Asp26Asp), rs2122195388, gnomAD 19-50398929-T-C, CADD 0.28
- D27G (p.Asp27Gly), rs150066950, ClinGen CA9595610, ClinVar RCV001768931, ClinVar RCV003640987, REVEL 0.05, CADD 14.50, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Colorectal cancer, susceptibility to, 1
- D27V (p.Asp27Val), rs150066950, ClinGen CA9595609, ClinVar RCV000235786, ClinVar RCV000415831, REVEL 0.06, CADD 17.60, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not specified; not provided
- p.Asp27dup, rs767241512, gnomAD 19-50398920-G-GGA, CADD 14.70
- D27del (p.Asp27del), rs767241512, gnomAD 19-50398920-GGAT-, CADD 14.40
- D27Y (p.Asp27Tyr), gnomAD 19-50398930-G-T, REVEL 0.09, CADD 20.30
- D27N (p.Asp27Asn), gnomAD 19-50398930-G-A, REVEL 0.07, CADD 16.90
- A28G (p.Ala28Gly), rs765097158, ClinGen CA406970107, ClinVar RCV002019798, ExAC rs765097158, REVEL 0.01, CADD 0.63, Uncertain significance, Colorectal cancer, susceptibility to, 10
- A28T (p.Ala28Thr), ExAC rs761551015, gnomAD rs761551015
- A28V (p.Ala28Val), rs765097158, ClinGen CA9595612, ClinVar RCV000537097, ClinVar RCV001764580, REVEL 0.03, CADD 1.48, Uncertain significance, not provided; Colorectal cancer, susceptibility to, 10; Hereditary cancer-predis
- A28S (p.Ala28Ser), gnomAD 19-50398933-G-T, REVEL 0.01, CADD 0.02
- A28E (p.Ala28Glu), gnomAD 19-50398934-C-A, REVEL 0.02, CADD 0.09
- P29H (p.Pro29His), cosmic curated COSV10148, REVEL 0.11, CADD 0.31
- P29L (p.Pro29Leu), gnomAD rs1361309144, REVEL 0.04, CADD 0.30
- P29S (p.Pro29Ser), rs750303995, ClinGen CA9595613, ClinVar RCV000471199, ClinVar RCV001551983, REVEL 0.01, CADD 3.46, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Colorectal cancer, suscep
- P29R (p.Pro29Arg), gnomAD 19-50398937-C-G, REVEL 0.05, CADD 0.21
- R30L (p.Arg30Leu), rs765969481, ClinGen CA9595614, ClinVar RCV001070665, ClinVar RCV002374995, REVEL 0.02, AlphaMissense 0.09, Uncertain significance, Colorectal cancer, susceptibility to, 10; Hereditary cancer-predisposing syndrom
- R30P (p.Arg30Pro), rs765969481, ClinGen CA406970115, ClinVar RCV001235797, ExAC rs765969481, AlphaMissense 0.09, MetaLR 0.01, Uncertain significance, Colorectal cancer, susceptibility to, 10
- R30Q (p.Arg30Gln), rs765969481, ClinGen CA406970114, cosmic curated COSV70956, ClinVar RCV000818343, REVEL 0.02, AlphaMissense 0.09, Conflicting interpretations, not provided; Hereditary cancer-predisposing syndrome; Colorectal cancer, suscep
- R30W (p.Arg30Trp), rs3218772, ClinGen CA348473, cosmic curated COSV70955, ClinVar RCV000204228, REVEL 0.03, CADD 19.20, Benign/Likely benign, Colorectal cancer, susceptibility to, 10; Mandibular hypoplasia-deafness-progero
- R30R (p.Arg30Arg), gnomAD 19-50398939-C-A, CADD 6.83
- P31L (p.Pro31Leu), rs2038475705, ClinGen CA406970121, ClinVar RCV001043038, ClinVar RCV002372775, REVEL 0.15, CADD 22.60, Uncertain significance, Hereditary cancer-predisposing syndrome; Colorectal cancer, susceptibility to, 1
- P31Q (p.Pro31Gln), rs2038475705, ClinGen CA406970119, ClinVar RCV002038940, Ensembl rs2038475705, REVEL 0.13, CADD 23.30, Uncertain significance, Colorectal cancer, susceptibility to, 10
- P31S (p.Pro31Ser), rs2513932760, ClinVar RCV004590610, REVEL 0.11, CADD 22.50, Uncertain significance, not provided
- P31T (p.Pro31Thr), gnomAD 19-50398942-C-A, REVEL 0.12, CADD 21.70
- P31P (p.Pro31Pro), gnomAD 19-50398944-A-T, CADD 1.75
- S32F (p.Ser32Phe), rs959521780, ClinGen CA406970126, ClinVar RCV000699121, ClinVar RCV001799702, REVEL 0.14, AlphaMissense 0.39, Uncertain significance, not provided; Colorectal cancer, susceptibility to, 10; Hereditary cancer-predis
- S32Y (p.Ser32Tyr), rs959521780, ClinGen CA309597856, ClinVar RCV000806489, ClinVar RCV002381777, AlphaMissense 0.39, MetaLR 0.03, Uncertain significance, Colorectal cancer, susceptibility to, 10; Hereditary cancer-predisposing syndrom
- S32I (p.Ser32Ile), rs1331967965, gnomAD 19-50398941-G-GC, CADD 23.10
- S32T (p.Ser32Thr), gnomAD 19-50398945-T-A, REVEL 0.10, CADD 20.60
- S32S (p.Ser32Ser), rs1555789086, gnomAD 19-50398947-C-A, CADD 4.18
- Q33* (p.Gln33Ter), rs1601189076, ClinGen CA406970127, ClinVar RCV001019767, ClinVar RCV003526030, CADD 40.00, Uncertain significance
- Q33H (p.Gln33His), ExAC rs751090809, gnomAD rs751090809, Likely benign
- Q33K (p.Gln33Lys), gnomAD 19-50398948-C-A, REVEL 0.05, CADD 18.10
- Q33R (p.Gln33Arg), gnomAD 19-50398949-A-G, REVEL 0.05, CADD 19.20
- Q33Q (p.Gln33Gln), rs751090809, gnomAD 19-50398950-A-G, CADD 10.50
- F34I (p.Phe34Ile), rs2038476429, ClinGen CA406970135, ClinVar RCV001038467, Ensembl rs2038476429, REVEL 0.09, CADD 22.40, Uncertain significance, Colorectal cancer, susceptibility to, 10
- F34L (p.Phe34Leu), rs754716741, ClinGen CA406970141, ClinVar RCV001043709, ClinVar RCV002379515, REVEL 0.17, CADD 7.25, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Colorectal cancer, susceptibility to, 1
- F34Y (p.Phe34Tyr), gnomAD 19-50398952-T-A, REVEL 0.08, CADD 21.60
- F34F (p.Phe34Phe), rs754716741, gnomAD 19-50398953-C-T, CADD 0.70
- E35K (p.Glu35Lys), rs554554906, ClinGen CA9595617, cosmic curated COSV70956, ClinVar RCV000463677, REVEL 0.19, CADD 25.30, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Colorectal cancer, suscep
- E35V (p.Glu35Val), rs1060501832, ClinGen CA16616104, ClinVar RCV000476945, ClinVar RCV001764403, AlphaMissense 0.75, MetaLR 0.02, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Colorectal cancer, suscep
- E35* (p.Glu35Ter), gnomAD 19-50398954-G-T, CADD 48.00
- E35E (p.Glu35Glu), gnomAD 19-50398956-G-A, CADD 4.84
- E36A (p.Glu36Ala), rs2513932899, ClinGen CA406970152, ClinVar RCV002424154, ClinVar RCV005097940, Uncertain significance, Hereditary cancer-predisposing syndrome; Colorectal cancer, susceptibility to, 1
- E36K (p.Glu36Lys), Ensembl rs2038477006, REVEL 0.09, CADD 23.20
- E36del (p.Glu36del), rs1555789096, gnomAD 19-50398953-CGAG-, CADD 22.10
- E36G (p.Glu36Gly), gnomAD 19-50398958-A-G, REVEL 0.03, CADD 23.80
- E36D (p.Glu36Asp), gnomAD 19-50398959-G-T, REVEL 0.02, CADD 19.90
- E36E (p.Glu36Glu), gnomAD 19-50398959-G-A, CADD 9.30
- D37E (p.Asp37Glu), rs1260697914, gnomAD rs1260697914, ClinGen CA406970162, ClinVar RCV003385766, REVEL 0.03, CADD 5.81, Likely benign, Hereditary cancer-predisposing syndrome
- D37G (p.Asp37Gly), cosmic curated COSV70956
- D37N (p.Asp37Asn), rs754269222, ClinGen CA9595618, ClinVar RCV001037683, ClinVar RCV002280150, REVEL 0.09, CADD 22.50, Uncertain significance, Hereditary cancer-predisposing syndrome; Colorectal cancer, susceptibility to, 1
- D37V (p.Asp37Val), gnomAD rs1486924942, REVEL 0.05, CADD 23.80
- D37T (p.Asp37Thr), gnomAD 19-50398958-AG-A, CADD 26.20
- D37D (p.Asp37Asp), rs1260697914, gnomAD 19-50398962-C-T, CADD 5.93
- L38Q (p.Leu38Gln), rs1601189190, ClinGen CA406970166, ClinVar RCV000815284, ClinVar RCV002453852, AlphaMissense 0.78, MetaLR 0.05, Uncertain significance, Colorectal cancer, susceptibility to, 10; Hereditary cancer-predisposing syndrom
- L38V (p.Leu38Val), rs1484596172, ClinGen CA406970165, ClinVar RCV001224296, TOPMed rs1484596172, REVEL 0.05, CADD 22.40, Uncertain significance, Colorectal cancer, susceptibility to, 10
- L38W (p.Leu38Trp), rs2038477468, gnomAD 19-50398961-AC-A, CADD 22.50
Public POLD1 analysis runs
- POLD1 analysis run — POLD1 (3,864 variants) — completed 2026-08-18