DNMT1 (P26358) variants and mutations
DNMT1 (also known as P26358) is a human protein-coding gene encoding a DNA (cytosine-5)-methyltransferase 1 protein. It copies existing DNA methylation patterns during replication and also contributes to chromatin regulation and neuronal maintenance. Dominant pathogenic variants can cause hereditary sensory neuropathy with dementia and hearing loss or a cerebellar ataxia-deafness-narcolepsy syndrome. This analysis covers 1,968 DNMT1 variants and mutations. Of these, 40% have computational variant effect predictions. Disease context includes autosomal dominant cerebellar ataxia, deafness and narcolepsy, hereditary sensory neuropathy-deafness-dementia syndrome, and acute myeloid leukemia. Example DNMT1 variants include M1?, P2A, and P2L.
Variant analysis overview
- Gene: DNMT1
- Protein: P26358
- UniProt accession: P26358
- Organism: Homo sapiens
- Variants analyzed: 1968
- Variant scope: all variants
- Completed: 2026-08-22
Variant and mutation evidence
- Variant composition: 1,762 unspecified-consequence records; 6 stop lost; 40 synonymous variants; 134 missense variants; 10 stop-gained variants; 15 frameshift variants; 3 in-frame deletions; 1 in-frame insertions; 1 stop retained variant; 1 splice-region variants; 3 substitution
- Prediction scores: 779 variants have prediction scores (40% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: autosomal dominant cerebellar ataxia, deafness and narcolepsy, hereditary sensory neuropathy-deafness-dementia syndrome, acute myeloid leukemia, myelodysplastic syndrome, cancer, chronic myelomonocytic leukemia, myelodysplastic syndrome with excess blasts, neoplasm, anemia, myeloid leukemia, deafness, neurodegenerative disease.
Protein structure and variant hotspots
- Protein features: 5 domains; 28 binding sites; 37 post-translational modification sites.
- Structural context: 1,085 variants have structural context.
- PTM context: 37 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, MaveDB, LitVar.
Notable DNMT1 variants
Examples include M1?, P2A, P2L, P2R, P2S, A3V, A6T, P7A. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, cosmic curated COSV61584
- P2A (p.Pro2Ala), ExAC rs763647098, gnomAD rs763647098, REVEL 0.15, CADD 26.90
- P2L (p.Pro2Leu), rs1248298976, ClinGen CA403950279, cosmic curated COSV61576, ClinVar RCV001039886, REVEL 0.23, CADD 32.00, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- P2R (p.Pro2Arg), TOPMed rs1248298976, Uncertain significance
- P2S (p.Pro2Ser), rs763647098, ClinGen CA403950282, ClinVar RCV003225556, ClinVar RCV005102419, REVEL 0.15, CADD 28.20, Uncertain significance, not provided; Hereditary sensory neuropathy-deafness-dementia syndrome
- A3V (p.Ala3Val), ExAC rs760288360, TOPMed rs760288360, gnomAD rs760288360, REVEL 0.14, CADD 32.00
- A6T (p.Ala6Thr), TOPMed rs1487433053, gnomAD rs1487433053, REVEL 0.16, CADD 23.90
- P7A (p.Pro7Ala), rs766984573, ClinGen CA403950254, ClinVar RCV003641677, AlphaMissense 0.31, MetaLR 0.08, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- P7L (p.Pro7Leu), Ensembl rs1599417000, REVEL 0.17, CADD 31.00
- P7S (p.Pro7Ser), rs766984573, ClinGen CA9188885, ClinVar RCV001866672, ExAC rs766984573, REVEL 0.13, AlphaMissense 0.31, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- A8G (p.Ala8Gly), rs994411260, ClinGen CA305193780, ClinVar RCV003852690, TOPMed rs994411260, AlphaMissense 0.21, MetaLR 0.07, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- A8P (p.Ala8Pro), TOPMed rs1217509888, gnomAD rs1217509888, Uncertain significance
- A8S (p.Ala8Ser), rs1217509888, ClinGen CA403950248, ClinVar RCV002755751, TOPMed rs1217509888, REVEL 0.08, CADD 24.40, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- R9G (p.Arg9Gly), TOPMed rs2039376099, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- R9L (p.Arg9Leu), cosmic curated COSV10053, REVEL 0.18, CADD 25.20
- R9Q (p.Arg9Gln), ExAC rs759577079, TOPMed rs759577079, gnomAD rs759577079, REVEL 0.10, CADD 28.80
- V10G (p.Val10Gly), rs2513933694, ClinGen CA403950236, ClinVar RCV002435612, Uncertain significance, Inborn genetic diseases
- V10L (p.Val10Leu), cosmic curated COSV10465
- V10M (p.Val10Met), TOPMed rs1269997956, gnomAD rs1269997956, REVEL 0.11, CADD 24.80
- P11A (p.Pro11Ala), rs1216341078, ClinGen CA403950234, ClinVar RCV002322954, AlphaMissense 0.14, MetaLR 0.04, Uncertain significance, Inborn genetic diseases
- P11S (p.Pro11Ser), cosmic curated COSV61579, gnomAD rs1216341078, REVEL 0.07, AlphaMissense 0.14
- T12A (p.Thr12Ala), TOPMed rs1170521928, CADD 16.60
- L13M (p.Leu13Met), ExAC rs762812098, TOPMed rs762812098, gnomAD rs762812098, REVEL 0.07, CADD 22.40
- L13Q (p.Leu13Gln), gnomAD rs1348019056, REVEL 0.18, CADD 24.00
- A14T (p.Ala14Thr), Ensembl rs2039375350, REVEL 0.13, CADD 24.80
- V15A (p.Val15Ala), rs1395421881, ClinGen CA403950210, ClinVar RCV001869959, gnomAD rs1395421881, REVEL 0.04, CADD 17.80, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- V15F (p.Val15Phe), ExAC rs769897113, TOPMed rs769897113, gnomAD rs769897113, REVEL 0.06, CADD 17.40
- V15I (p.Val15Ile), ExAC rs769897113, TOPMed rs769897113, gnomAD rs769897113, REVEL 0.03, CADD 12.20
- P16L (p.Pro16Leu), rs1476955893, ClinGen CA403950203, cosmic curated COSV61584, ClinVar RCV002745489, REVEL 0.05, CADD 19.10, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- P16Q (p.Pro16Gln), TOPMed rs1476955893, gnomAD rs1476955893, REVEL 0.04, CADD 19.20, Uncertain significance
- P16S (p.Pro16Ser), TOPMed rs1324769959, CADD 10.30
- P16T (p.Pro16Thr), cosmic curated COSV10053, CADD 9.83
- A17T (p.Ala17Thr), cosmic curated COSV61577, REVEL 0.15, CADD 26.20
- A17V (p.Ala17Val), ExAC rs768745074, TOPMed rs768745074, gnomAD rs768745074, REVEL 0.13, CADD 27.20
- I18F (p.Ile18Phe), TOPMed rs1759690595, gnomAD rs1759690595, REVEL 0.09, CADD 16.50
- S19L (p.Ser19Leu), rs747559452, ClinGen CA9188875, ClinVar RCV000414738, ClinVar RCV000806365, REVEL 0.13, CADD 24.00, Uncertain significance, not provided; Hereditary sensory neuropathy-deafness-dementia syndrome
- S19P (p.Ser19Pro), rs2513933553, ClinGen CA403950189, ClinVar RCV003642018, REVEL 0.17, CADD 25.20, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- P21A (p.Pro21Ala), rs2145417655, ClinGen CA403950179, ClinVar RCV001965678, Ensembl rs2145417655, AlphaMissense 0.53, MetaLR 0.72, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- P21L (p.Pro21Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- D22N (p.Asp22Asn), rs1224343919, ClinGen CA403950173, ClinVar RCV002364133, TOPMed rs1224343919, REVEL 0.14, CADD 29.40, Uncertain significance, Inborn genetic diseases
- D23N (p.Asp23Asn), rs1257821053, gnomAD rs1257821053, REVEL 0.15, CADD 23.10, Uncertain significance, not provided; Hereditary sensory neuropathy-deafness-dementia syndrome
- V24I (p.Val24Ile), TOPMed rs1271779036
- R25C (p.Arg25Cys), gnomAD rs1206120198, REVEL 0.39, CADD 32.00
- R26K (p.Arg26Lys), TOPMed rs1340824034, REVEL 0.15, CADD 23.30
- R26S (p.Arg26Ser), rs780503694, ClinGen CA9188874, ClinVar RCV000649353, ClinVar RCV004025778, REVEL 0.15, CADD 24.50, Uncertain significance, Inborn genetic diseases; Hereditary sensory neuropathy-deafness-dementia syndrom
- R27=, NCI-TCGA TCGA novel, Variant assessed as somatic; low impact.
- R27Q (p.Arg27Gln), rs753721329, ClinGen CA9188873, ClinVar RCV003641183, ClinVar RCV003939131, REVEL 0.31, CADD 35.00, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- L28F (p.Leu28Phe), cosmic curated COSV10816
- L28I (p.Leu28Ile), Ensembl rs2145383071
- R33G (p.Arg33Gly), rs374817622, ClinGen CA9188846, ClinVar RCV001236858, ESP rs374817622, REVEL 0.17, CADD 23.40, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- D34G (p.Asp34Gly), rs2039056533, ClinGen CA403948232, ClinVar RCV002031912, TOPMed rs2039056533, REVEL 0.13, CADD 23.20, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- D34N (p.Asp34Asn), Ensembl rs2039056589
- S35N (p.Ser35Asn), ExAC rs751109006, gnomAD rs751109006, REVEL 0.08, CADD 13.80, Likely benign, Hereditary sensory neuropathy-deafness-dementia syndrome
- L36V (p.Leu36Val), rs1300001842, ClinGen CA403948188, ClinVar RCV003528904, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- E38* (p.Glu38Ter), NCI-TCGA Cosmic COSV6158, cosmic curated COSV61580, Variant assessed as somatic; high impact.
- E38A (p.Glu38Ala), cosmic curated COSV61584
- E38K (p.Glu38Lys), gnomAD rs1379799242
- C41R (p.Cys41Arg), rs1218241317, ClinGen CA403947348, ClinVar RCV003642330, gnomAD rs1218241317, REVEL 0.20, CADD 24.50, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- C41W (p.Cys41Trp), ExAC rs779730617, gnomAD rs779730617, REVEL 0.33, CADD 22.30
- V42E (p.Val42Glu), TOPMed rs2039033590
- K43R (p.Lys43Arg), gnomAD rs1264838175, REVEL 0.06, CADD 22.70, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- E44* (p.Glu44Ter), cosmic curated COSV10465
- E44K (p.Glu44Lys), gnomAD rs1242559756, REVEL 0.14, CADD 24.30
- K45Q (p.Lys45Gln), cosmic curated COSV61576
- K45R (p.Lys45Arg), ExAC rs757938210, gnomAD rs757938210, REVEL 0.25, CADD 28.00
- L46F (p.Leu46Phe), gnomAD rs1234060339, REVEL 0.23, CADD 24.70
- L46S (p.Leu46Ser), cosmic curated COSV10886
- L48I (p.Leu48Ile), rs2145379887, ClinGen CA403947275, ClinVar RCV001925968, Ensembl rs2145379887, AlphaMissense 0.14, MetaLR 0.29, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- L48V (p.Leu48Val), NCI-TCGA Cosmic COSV6158, cosmic curated COSV61580, REVEL 0.39, CADD 24.50, Variant assessed as somatic; moderate impact.
- H50Q (p.His50Gln), rs146112081, ClinGen CA403947246, ClinVar RCV001925550, 1000Genomes rs146112081, REVEL 0.11, CADD 14.00, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- H50Y (p.His50Tyr), rs2039033115, ClinGen CA403947252, ClinVar RCV001068228, Ensembl rs2039033115, AlphaMissense 0.18, MetaLR 0.10, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- E51D (p.Glu51Asp), rs1401965330, ClinGen CA403947231, ClinVar RCV003041155, TOPMed rs1401965330, REVEL 0.14, CADD 22.40, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- E51K (p.Glu51Lys), rs755995375, ClinGen CA9188822, NCI-TCGA Cosmic COSV6157, cosmic curated COSV61576, REVEL 0.22, CADD 24.80, Conflicting interpretations, Hereditary sensory neuropathy-deafness-dementia syndrome; not provided
- Q54* (p.Gln54Ter), gnomAD rs1361282395
- T55A (p.Thr55Ala), rs375585911, ClinGen CA9188821, ClinVar RCV001230908, ESP rs375585911, REVEL 0.10, CADD 22.80, Likely benign, Hereditary sensory neuropathy-deafness-dementia syndrome
- E56* (p.Glu56Ter), NCI-TCGA Cosmic COSV6158, cosmic curated COSV61583, CADD 38.00, Variant assessed as somatic; high impact.
- K58N (p.Lys58Asn), cosmic curated COSV10968
- K58Q (p.Lys58Gln), rs2145379807, ClinGen CA403947159, ClinVar RCV001371406, Ensembl rs2145379807, AlphaMissense 0.14, MetaLR 0.09, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- N59D (p.Asn59Asp), rs2039032693, ClinGen CA403947146, ClinVar RCV001346906, Ensembl rs2039032693, REVEL 0.14, CADD 20.70, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- N59K (p.Asn59Lys), gnomAD rs1351910032, REVEL 0.11, CADD 21.60, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- Q60E (p.Gln60Glu), cosmic curated COSV61580
- Q60H (p.Gln60His), Ensembl rs2039032568
- C62R (p.Cys62Arg), rs2513894358, ClinGen CA403947111, ClinVar RCV003875357, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- E65* (p.Glu65Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- R69C (p.Arg69Cys), rs753673660, ClinGen CA9188820, ClinVar RCV001219887, ExAC rs753673660, REVEL 0.14, CADD 25.40, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- R69G (p.Arg69Gly), rs753673660, ClinGen CA403947034, ClinVar RCV002947207, REVEL 0.06, CADD 26.00, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- R69H (p.Arg69His), rs61750053, ClinGen CA290655, cosmic curated COSV61577, ClinVar RCV000124761, REVEL 0.04, CADD 15.50, Benign, not specified; not provided; Hereditary sensory neuropathy-deafness-dementia syn
- R69L (p.Arg69Leu), rs61750053, ClinGen CA403947028, ClinVar RCV001058476, 1000Genomes rs61750053, REVEL 0.04, CADD 19.40, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- K70E (p.Lys70Glu), rs2513894206, ClinGen CA403947025, ClinVar RCV003880013, REVEL 0.21, CADD 24.30, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- K70N (p.Lys70Asn), cosmic curated COSV10523
- K70T (p.Lys70Thr), TOPMed rs1279416770
- E71G (p.Glu71Gly), rs1477841278, ClinGen CA403947011, ClinVar RCV002938554, gnomAD rs1477841278, REVEL 0.22, CADD 29.80, Likely benign, Hereditary sensory neuropathy-deafness-dementia syndrome
- E71K (p.Glu71Lys), cosmic curated COSV61577
- S74F (p.Ser74Phe), NCI-TCGA Cosmic COSV1005, cosmic curated COSV10053, Variant assessed as somatic; moderate impact.
- E75K (p.Glu75Lys), rs1206145138, ClinGen CA403946972, cosmic curated COSV10647, ClinVar RCV001797484, AlphaMissense 0.35, MetaLR 0.21, Uncertain significance, not provided
- G77A (p.Gly77Ala), rs984728792, ClinGen CA305185046, ClinVar RCV003056531, TOPMed rs984728792, REVEL 0.19, CADD 23.10, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- G77R (p.Gly77Arg), rs746687493, ClinGen CA305185047, ClinVar RCV001224274, ClinVar RCV005909057, REVEL 0.31, CADD 23.50, Conflicting interpretations, not specified; Hereditary sensory neuropathy-deafness-dementia syndrome
- G77S (p.Gly77Ser), rs746687493, ClinGen CA9188808, ClinVar RCV000692609, ClinVar RCV002442450, REVEL 0.27, CADD 23.50, Conflicting interpretations, Inborn genetic diseases; Hereditary sensory neuropathy-deafness-dementia syndrom
- G77V (p.Gly77Val), TOPMed rs984728792, gnomAD rs984728792, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- Y78F (p.Tyr78Phe), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L79P (p.Leu79Pro), NCI-TCGA Cosmic COSV1005, cosmic curated COSV10053, Variant assessed as somatic; moderate impact.
- L79V (p.Leu79Val), TOPMed rs1233113560, gnomAD rs1233113560
- A80D (p.Ala80Asp), TOPMed rs2039027518
- V82A (p.Val82Ala), NCI-TCGA Cosmic COSV6157, cosmic curated COSV61578, Variant assessed as somatic; moderate impact.
- S84C (p.Ser84Cys), NCI-TCGA Cosmic COSV6158, cosmic curated COSV61580, Variant assessed as somatic; moderate impact.
- S84F (p.Ser84Phe), NCI-TCGA Cosmic COSV6158, REVEL 0.16, CADD 24.90, Variant assessed as somatic; moderate impact.
- S84Y (p.Ser84Tyr), cosmic curated COSV10610, REVEL 0.18, CADD 26.30
- N87S (p.Asn87Ser), Ensembl rs953187775
- K88E (p.Lys88Glu), TOPMed rs1456240920, gnomAD rs1456240920, REVEL 0.24, CADD 24.40
- D89Y (p.Asp89Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L90V (p.Leu90Val), rs779818604, ExAC rs779818604, TOPMed rs779818604, gnomAD rs779818604, REVEL 0.17, CADD 24.40, Variant assessed as somatic; moderate impact.
- S91F (p.Ser91Phe), TOPMed rs1268674999, cosmic curated COSV10886, REVEL 0.26, CADD 23.40
- L92F (p.Leu92Phe), cosmic curated COSV61576
- E93V (p.Glu93Val), NCI-TCGA Cosmic COSV1005, cosmic curated COSV10053, Variant assessed as somatic; moderate impact.
- N94D (p.Asn94Asp), ExAC rs778222019, gnomAD rs778222019, REVEL 0.23, CADD 26.30
- G95S (p.Gly95Ser), TOPMed rs2039026843, gnomAD rs2039026843, REVEL 0.22, CADD 25.50
- A96G (p.Ala96Gly), TOPMed rs2039026701, gnomAD rs2039026701
- A96P (p.Ala96Pro), TOPMed rs1338494594, gnomAD rs1338494594
- A96V (p.Ala96Val), TOPMed rs2039026701, gnomAD rs2039026701, REVEL 0.09, CADD 21.30
- H97R (p.His97Arg), rs16999593, ClinGen CA9188801, cosmic curated COSV61577, ClinVar RCV000246863, REVEL 0.02, CADD 12.10, Benign, not specified; not provided; Hereditary sensory neuropathy-deafness-dementia syn
- H97Y (p.His97Tyr), rs753670606, ClinGen CA9188802, ClinVar RCV002438018, ClinVar RCV003528401, REVEL 0.13, CADD 20.70, Uncertain significance, Inborn genetic diseases; Hereditary sensory neuropathy-deafness-dementia syndrom
- A98S (p.Ala98Ser), ExAC rs755873606, gnomAD rs755873606, REVEL 0.04, CADD 7.61, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- N100I (p.Asn100Ile), gnomAD rs1375073063, Uncertain significance
- N100K (p.Asn100Lys), ExAC rs752966527, gnomAD rs752966527, REVEL 0.03, CADD 6.43
- N100S (p.Asn100Ser), rs1375073063, ClinGen CA403946565, ClinVar RCV000649354, gnomAD rs1375073063, REVEL 0.06, CADD 0.68, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- N100Y (p.Asn100Tyr), rs2513892895, ClinGen CA403946576, ClinVar RCV003857530, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- R101Q (p.Arg101Gln), rs1401130665, ClinGen CA403946553, ClinVar RCV000703179, TOPMed rs1401130665, REVEL 0.09, CADD 13.20, Likely benign, Hereditary sensory neuropathy-deafness-dementia syndrome
- R101W (p.Arg101Trp), rs369196079, ClinGen CA9188798, cosmic curated COSV61583, ClinVar RCV000700835, REVEL 0.15, CADD 24.10, Conflicting interpretations, Inborn genetic diseases; not provided; Hereditary sensory neuropathy-deafness-de
- E102* (p.Glu102Ter), cosmic curated COSV61584
- E102D (p.Glu102Asp), cosmic curated COSV61579
- E102G (p.Glu102Gly), cosmic curated COSV61584
- E102Q (p.Glu102Gln), TOPMed rs1039555172
- N104D (p.Asn104Asp), gnomAD rs1170262960, REVEL 0.14, CADD 24.80
- N104I (p.Asn104Ile), cosmic curated COSV10743
- G105E (p.Gly105Glu), cosmic curated COSV61583, REVEL 0.22, CADD 24.20
- R106C (p.Arg106Cys), rs759600542, ClinGen CA9188797, NCI-TCGA Cosmic COSV1005, cosmic curated COSV10053, REVEL 0.03, CADD 11.50, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- R106H (p.Arg106His), rs751662619, ClinGen CA9188796, cosmic curated COSV10441, ClinVar RCV001910372, REVEL 0.06, CADD 10.90, Conflicting interpretations, Hereditary sensory neuropathy-deafness-dementia syndrome; not provided
- R106L (p.Arg106Leu), ExAC rs751662619, gnomAD rs751662619, Uncertain significance
- E108Q (p.Glu108Gln), cosmic curated COSV61584
- N109D (p.Asn109Asp), gnomAD rs1157913728
- G110R (p.Gly110Arg), rs376894659, ClinGen CA9188794, cosmic curated COSV61584, ClinVar RCV000555892, REVEL 0.16, CADD 24.40, Uncertain significance, Inborn genetic diseases; Hereditary sensory neuropathy-deafness-dementia syndrom
- G110W (p.Gly110Trp), cosmic curated COSV10465
- N111I (p.Asn111Ile), rs906790753, ClinGen CA403946389, ClinVar RCV003641415, AlphaMissense 0.05, MetaLR 0.01, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- N111K (p.Asn111Lys), ExAC rs770318428, TOPMed rs770318428, gnomAD rs770318428, REVEL 0.05, CADD 14.60, Likely benign
- N111S (p.Asn111Ser), rs906790753, ClinGen CA305185005, ClinVar RCV001370589, TOPMed rs906790753, REVEL 0.02, AlphaMissense 0.05, Likely benign, Hereditary sensory neuropathy-deafness-dementia syndrome
- A113G (p.Ala113Gly), ExAC rs762241565, gnomAD rs762241565, REVEL 0.01, CADD 5.46
- R114I (p.Arg114Ile), NCI-TCGA Cosmic COSV1005, cosmic curated COSV10053, Variant assessed as somatic; moderate impact.
- R114K (p.Arg114Lys), rs554894511, ClinGen CA9188790, cosmic curated COSV61580, ClinVar RCV000235913, REVEL 0.04, CADD 10.40, Uncertain significance, Inborn genetic diseases; not provided; Hereditary sensory neuropathy-deafness-de
- R118C (p.Arg118Cys), rs745455817, ClinGen CA9188788, cosmic curated COSV10968, ClinVar RCV002953634, REVEL 0.01, CADD 6.78, Likely benign, Hereditary sensory neuropathy-deafness-dementia syndrome
- R118H (p.Arg118His), rs149362098, ClinGen CA9188787, cosmic curated COSV10053, ClinVar RCV001899700, REVEL 0.09, CADD 12.10, Likely benign, Hereditary sensory neuropathy-deafness-dementia syndrome
- R118L (p.Arg118Leu), rs149362098, ClinGen CA403946320, cosmic curated COSV61577, ClinVar RCV001323725, REVEL 0.03, CADD 6.72, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- R119G (p.Arg119Gly), rs146516082, ClinGen CA9188785, ClinVar RCV001214584, ClinVar RCV001815026, REVEL 0.01, CADD 11.80, Uncertain significance, not specified; Hereditary sensory neuropathy-deafness-dementia syndrome; Inborn
- R119S (p.Arg119Ser), rs373923585, ClinGen CA9188783, ClinVar RCV001056097, ClinVar RCV002460128, REVEL 0.01, CADD 5.75, Conflicting interpretations, Hereditary sensory neuropathy-deafness-dementia syndrome; Inborn genetic disease
- R119T (p.Arg119Thr), ExAC rs777666240, gnomAD rs777666240, REVEL 0.04, CADD 8.24
- V120L (p.Val120Leu), rs75616428, ClinGen CA9188782, cosmic curated COSV10743, ClinVar RCV000543299, REVEL 0.02, CADD 6.01, Benign, Hereditary sensory neuropathy-deafness-dementia syndrome; not specified; not pro
- G121E (p.Gly121Glu), gnomAD rs1397430053, REVEL 0.03, CADD 0.00
- G121R (p.Gly121Arg), gnomAD rs1331733943, REVEL 0.01, CADD 0.52
- M122V (p.Met122Val), ExAC rs780782457, gnomAD rs780782457
- A123G (p.Ala123Gly), rs1085307725, ClinGen CA403946273, ClinVar RCV000490029, TOPMed rs1085307725, REVEL 0.02, CADD 17.30, Uncertain significance, not provided
- A123T (p.Ala123Thr), TOPMed rs2039024197, REVEL 0.03, CADD 15.20
- D124C (p.Asp124Cys), cosmic curated COSV61584
- D124H (p.Asp124His), NCI-TCGA Cosmic COSV1005, cosmic curated COSV10053, Variant assessed as somatic; moderate impact.
- D124N (p.Asp124Asn), NCI-TCGA Cosmic COSV1005, Variant assessed as somatic; moderate impact.
- D124V (p.Asp124Val), rs2513892575, ClinGen CA403946263, ClinVar RCV003528882, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- A125T (p.Ala125Thr), rs1417767085, ClinGen CA403946259, ClinVar RCV003129082, gnomAD rs1417767085, REVEL 0.03, CADD 3.02, Uncertain significance, not provided
- A125V (p.Ala125Val), rs2039023989, ClinGen CA403946251, ClinVar RCV001067191, TOPMed rs2039023989, REVEL 0.05, CADD 13.20, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- N126H (p.Asn126His), TOPMed rs2039023874, REVEL 0.01, CADD 5.78
- N126T (p.Asn126Thr), ExAC rs751681312, gnomAD rs751681312, REVEL 0.01, CADD 4.47
- S127G (p.Ser127Gly), gnomAD rs2039023676, REVEL 0.04, CADD 9.03
- P128A (p.Pro128Ala), cosmic curated COSV10743, ESP rs146601335, ExAC rs146601335, TOPMed rs146601335, REVEL 0.01, CADD 1.50, Likely benign
- P128L (p.Pro128Leu), gnomAD rs1425787169, REVEL 0.14, CADD 16.60
- P128R (p.Pro128Arg), gnomAD rs1425787169, REVEL 0.16, CADD 16.40
- P128S (p.Pro128Ser), rs146601335, ClinGen CA9188776, ClinVar RCV000649363, ClinVar RCV002358866, REVEL 0.02, CADD 0.37, Conflicting interpretations, Inborn genetic diseases; Autosomal dominant cerebellar ataxia, deafness and narc
- P128T (p.Pro128Thr), rs146601335, ClinGen CA9188775, cosmic curated COSV61582, ClinVar RCV000235285, REVEL 0.01, CADD 1.75, Conflicting interpretations, Inborn genetic diseases; not provided; not specified
- P129A (p.Pro129Ala), rs1085307715, ClinGen CA403946216, ClinVar RCV003033788, gnomAD rs1085307715, REVEL 0.01, CADD 1.76, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- P129H (p.Pro129His), ESP rs370207020, ExAC rs370207020, TOPMed rs370207020, gnomAD rs370207020, REVEL 0.12, AlphaMissense 0.08, Uncertain significance
- P129L (p.Pro129Leu), rs370207020, ClinGen CA403946211, cosmic curated COSV61579, ClinVar RCV003529251, AlphaMissense 0.08, MetaLR 0.07, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- P129R (p.Pro129Arg), rs370207020, ClinGen CA9188772, ClinVar RCV003095819, ESP rs370207020, REVEL 0.08, AlphaMissense 0.08, Uncertain significance, Hereditary sensory neuropathy-deafness-dementia syndrome
- P129S (p.Pro129Ser), gnomAD rs1085307715, Uncertain significance
- P129T (p.Pro129Thr), rs1085307715, ClinGen CA403946214, ClinVar RCV000489739, gnomAD rs1085307715, REVEL 0.02, CADD 4.00, Uncertain significance, not provided
Public DNMT1 analysis runs
- DNMT1 analysis run — DNMT1 (1,968 variants) — completed 2026-08-22