SMC1A (Q14683) variants and mutations
SMC1A (also known as Q14683) is a human protein-coding gene encoding a structural maintenance of chromosomes protein 1A protein. A core cohesin protein that helps hold sister chromatids together and organize DNA. Variants can cause Cornelia de Lange syndrome or developmental epilepsy. This analysis covers 782 SMC1A variants and mutations. Of these, 88% have computational variant effect predictions. Disease context includes Cornelia de Lange syndrome, genetic developmental and epileptic encephalopathy, and hereditary disease. Example SMC1A variants include G2R, L4V, and F12V.
Variant analysis overview
- Gene: SMC1A
- Protein: Q14683
- UniProt accession: Q14683
- Organism: Homo sapiens
- Variants analyzed: 782
- Variant scope: all variants
- Completed: 2026-10-09
Variant and mutation evidence
- Variant composition: 731 unspecified-consequence records; 1 stop lost; 10 stop-gained variants; 82 missense variants; 1 in-frame deletions; 70 synonymous variants; 4 splice-region variants; 1 protein altering variant; 4 frameshift variants; 3 substitution
- Prediction scores: 688 variants have prediction scores (88% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Cornelia de Lange syndrome, genetic developmental and epileptic encephalopathy, hereditary disease, Epileptic encephalopathy, atypical Rett syndrome, Wiedemann-Steiner syndrome, microcephaly, X-linked complex neurodevelopmental disorder, Global developmental delay, semilobar holoprosencephaly, Seizure, Abnormal heart valve morphology.
Protein structure and variant hotspots
- Protein features: 1 domains; 1 binding sites; 9 post-translational modification sites.
- Structural context: 57 variants have structural context.
- PTM context: 5 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.
Diseases linked to SMC1A
Notable SMC1A variants
Examples include G2R, L4V, F12V, K13Q, S14L, K16E, R18*, I20T. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- G2R (p.Gly2Arg), rs2075764895, ClinGen CA413135787, ClinVar RCV003041671, Ensembl rs2075764895, ESM-1b 1.00, AlphaMissense 0.99, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome
- L4V (p.Leu4Val), Ensembl rs2075764867, ESM-1b 1.00, AlphaMissense 0.77
- F12V (p.Phe12Val), rs2146614101, ClinGen CA413135620, ClinVar RCV001990963, Ensembl rs2146614101, ESM-1b 1.00, AlphaMissense 1.00, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome
- K13Q (p.Lys13Gln), rs2075764777, ClinGen CA413135601, ClinVar RCV001055709, Ensembl rs2075764777, ESM-1b 1.00, AlphaMissense 1.00, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome
- S14L (p.Ser14Leu), rs2521010433, ClinGen CA413135573, ClinVar RCV003229431, ESM-1b 1.00, AlphaMissense 1.00, Likely pathogenic, not provided
- K16E (p.Lys16Glu), TOPMed rs2075764671, ESM-1b 1.00, AlphaMissense 0.93, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome
- R18* (p.Arg18Ter), rs2521010322, ClinGen CA413135515, ClinVar RCV003624097, CADD 35.00, Pathogenic
- I20T (p.Ile20Thr), rs2521010247, ClinGen CA413134990, ClinVar RCV003416951, ESM-1b 0.00, AlphaMissense 0.26, Uncertain significance, SMC1A-related disorder
- G22R (p.Gly22Arg), Ensembl rs2075764597, ESM-1b 1.00, AlphaMissense 1.00, Uncertain significance, not provided
- T28P (p.Thr28Pro), rs34530151, UniProt VAR 052438, Ensembl rs34530151, ESM-1b 1.00, AlphaMissense 0.99
- I30V (p.Ile30Val), rs1330260800, ClinGen CA413134840, ClinVar RCV003988514, TOPMed rs1330260800, REVEL 0.24, ESM-1b 0.00, Uncertain significance, not specified
- I31T (p.Ile31Thr), Ensembl rs2075764440, REVEL 0.61, ESM-1b 1.00
- G32C (p.Gly32Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G32E (p.Gly32Glu), rs1556892359, ClinGen CA500024, ClinVar RCV000660365, Ensembl rs1556892359, ESM-1b 1.00, AlphaMissense 1.00, Likely pathogenic, Congenital muscular hypertrophy-cerebral syndrome
- G35D (p.Gly35Asp), 1000Genomes rs200998508, ExAC rs200998508, gnomAD rs200998508, REVEL 0.93, ESM-1b 1.00
- G37V (p.Gly37Val), rs1569359540, ClinGen CA413133217, ClinVar RCV000680258, ClinVar RCV005900097, ESM-1b 1.00, AlphaMissense 1.00, Likely pathogenic, Congenital muscular hypertrophy-cerebral syndrome
- S39* (p.Ser39Ter), rs1057518670, ClinGen CA16043711, ClinVar RCV000415358, Ensembl rs1057518670, Pathogenic
- L41F (p.Leu41Phe), rs727503776, ClinGen CA333597, ClinVar RCV000157052, Ensembl rs727503776, ESM-1b 1.00, AlphaMissense 0.91, Pathogenic
- M42V (p.Met42Val), rs1556891104, ClinGen CA413133133, ClinVar RCV000500991, Ensembl rs1556891104, ESM-1b 1.00, AlphaMissense 0.97, Conflicting interpretations, Congenital muscular hypertrophy-cerebral syndrome
- D43N (p.Asp43Asn), rs2520971102, ClinGen CA413133108, ClinVar RCV004798963, ESM-1b 1.00, AlphaMissense 1.00, Likely pathogenic, Congenital muscular hypertrophy-cerebral syndrome
- D43V (p.Asp43Val), rs1569359535, ClinGen CA413133099, ClinVar RCV000680259, Ensembl rs1569359535, ESM-1b 1.00, AlphaMissense 1.00, Likely pathogenic, Congenital muscular hypertrophy-cerebral syndrome
- F47C (p.Phe47Cys), rs1569359530, ClinGen CA413133027, ClinVar RCV000679805, Ensembl rs1569359530, ESM-1b 1.00, AlphaMissense 1.00, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome
- T53C (p.Thr53Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- N55K (p.Asn55Lys), gnomAD rs2075726974, REVEL 0.26, ESM-1b 1.00
- R62Q (p.Arg62Gln), rs2146606711, ClinGen CA413132707, cosmic curated COSV10439, ClinVar RCV001755214, ESM-1b 0.87, AlphaMissense 0.36, Uncertain significance, not provided
- I65V (p.Ile65Val), TOPMed rs1253441028, ESM-1b 1.00, AlphaMissense 0.41
- A75T (p.Ala75Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- N76S (p.Asn76Ser), rs200243549, ClinGen CA10420694, cosmic curated COSV10962, ClinVar RCV000687190, REVEL 0.13, ESM-1b 0.00, Likely benign, Congenital muscular hypertrophy-cerebral syndrome
- M82V (p.Met82Val), rs2146606672, ClinGen CA413132342, ClinVar RCV001532689, ClinVar RCV006650912, ESM-1b 0.00, AlphaMissense 0.25, Conflicting interpretations, not provided; Congenital muscular hypertrophy-cerebral syndrome
- S85C (p.Ser85Cys), TOPMed rs918387605, gnomAD rs918387605, REVEL 0.19, ESM-1b 0.00, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome; Developmental and epileptic e
- E90D (p.Glu90Asp), rs781811085, ClinGen CA10420693, ClinVar RCV002895150, ExAC rs781811085, REVEL 0.07, ESM-1b 0.00, Benign, Congenital muscular hypertrophy-cerebral syndrome
- R92C (p.Arg92Cys), rs1444762600, ClinGen CA413132140, cosmic curated COSV10605, ClinVar RCV004546172, REVEL 0.31, ESM-1b 1.00, Conflicting interpretations, not provided; Congenital muscular hypertrophy-cerebral syndrome
- R92H (p.Arg92His), ExAC rs782788649, REVEL 0.27, ESM-1b 0.61, Uncertain significance
- R92P (p.Arg92Pro), rs782788649, ClinGen CA413132131, ClinVar RCV002439479, ESM-1b 1.00, AlphaMissense 0.14, Uncertain significance, Inborn genetic diseases
- A95V (p.Ala95Val), Ensembl rs2075726675, REVEL 0.27, ESM-1b 1.00
- A95G (p.Ala95Gly), NCI-TCGA Cosmic COSV5912, Variant assessed as somatic; moderate impact.
- R96C (p.Arg96Cys), rs2146606642, ClinGen CA413132054, ClinVar RCV001940623, Ensembl rs2146606642, ESM-1b 1.00, AlphaMissense 1.00, Pathogenic, Congenital muscular hypertrophy-cerebral syndrome
- R96H (p.Arg96His), rs781817340, NCI-TCGA Cosmic COSV5912, cosmic curated COSV59128, 1000Genomes rs781817340, REVEL 0.71, ESM-1b 1.00, Likely pathogenic
- R96P (p.Arg96Pro), rs781817340, ClinGen CA413132052, ClinVar RCV000731943, 1000Genomes rs781817340, ESM-1b 1.00, AlphaMissense 1.00, Likely pathogenic, not provided
- G100R (p.Gly100Arg), rs1569359487, ClinGen CA413132013, ClinVar RCV000679806, Ensembl rs1569359487, ESM-1b 1.00, AlphaMissense 0.97, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome
- S102A (p.Ser102Ala), rs2146606564, ClinGen CA413131900, ClinVar RCV001371240, ClinVar RCV005423979, ESM-1b 1.00, AlphaMissense 0.13, Uncertain significance, not provided; Congenital muscular hypertrophy-cerebral syndrome
- S103C (p.Ser103Cys), Ensembl rs1215384023, ESM-1b 1.00, AlphaMissense 0.64
- E104G (p.Glu104Gly), rs1556891059, ClinGen CA413131844, ClinVar RCV000498677, Ensembl rs1556891059, ESM-1b 1.00, AlphaMissense 0.93, Likely pathogenic, not provided
- E104K (p.Glu104Lys), rs2075726145, ClinGen CA413131856, ClinVar RCV001267109, Ensembl rs2075726145, ESM-1b 1.00, AlphaMissense 0.95, Uncertain significance, Inborn genetic diseases
- K106R (p.Lys106Arg), ExAC rs782607829, gnomAD rs782607829, REVEL 0.13, ESM-1b 0.00
- N108S (p.Asn108Ser), Ensembl rs113068546, ESM-1b 1.00, AlphaMissense 0.17
- V111A (p.Val111Ala), gnomAD rs1556891055, REVEL 0.34, ESM-1b 0.91
- V111L (p.Val111Leu), Ensembl rs2075726063, ESM-1b 0.54, AlphaMissense 0.32
- H115P (p.His115Pro), TOPMed rs782554846, REVEL 0.27, ESM-1b 0.00
- L124* (p.Leu124Ter), rs1556891045, ClinGen CA413131522, ClinVar RCV003009631, AlphaMissense 0.85, MetaLR 0.23, Pathogenic
- L124F (p.Leu124Phe), rs148835205, ClinGen CA10420678, ClinVar RCV000976394, ClinVar RCV001456061, REVEL 0.21, ESM-1b 1.00, Likely benign, SMC1A-related disorder; Congenital muscular hypertrophy-cerebral syndrome; Devel
- L124S (p.Leu124Ser), gnomAD rs1556891045, REVEL 0.52, ESM-1b 1.00, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome
- G125A (p.Gly125Ala), rs2520969372, ClinGen CA2579615972, ClinVar RCV003009630, ESM-1b 1.00, AlphaMissense 0.86, Pathogenic
- I128T (p.Ile128Thr), Ensembl rs781895092, REVEL 0.25, ESM-1b 1.00
- K129R (p.Lys129Arg), rs1223252947, ClinGen CA413131457, cosmic curated COSV59132, ClinVar RCV001987995, REVEL 0.67, ESM-1b 1.00, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome; not specified
- R131C (p.Arg131Cys), rs2520969249, ClinGen CA413131436, ClinVar RCV003055605, REVEL 0.61, ESM-1b 1.00, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome
- R131H (p.Arg131His), rs781903928, ClinGen CA10420676, cosmic curated COSV10881, ClinVar RCV001059173, REVEL 0.51, ESM-1b 1.00, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome
- F133V (p.Phe133Val), rs2075725792, ClinGen CA413131409, ClinVar RCV001048385, UniProt VAR 062786, ESM-1b 1.00, AlphaMissense 0.99, Pathogenic, Congenital muscular hypertrophy-cerebral syndrome
- G138T (p.Gly138Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G138D (p.Gly138Asp), rs1569359134, ClinGen CA413259596, ClinVar RCV000721092, Ensembl rs1569359134, ESM-1b 1.00, AlphaMissense 1.00, Uncertain significance, History of neurodevelopmental disorder
- G138A (p.Gly138Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E141K (p.Glu141Lys), rs587784420, ClinGen CA272583, cosmic curated COSV59131, ClinVar RCV000147569, ESM-1b 1.00, AlphaMissense 1.00, Pathogenic, in CDLS2
- I143S (p.Ile143Ser), rs2146605688, ClinGen CA413259563, ClinVar RCV001942558, Ensembl rs2146605688, ESM-1b 1.00, AlphaMissense 1.00, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome
- I143V (p.Ile143Val), TOPMed rs1259197736, gnomAD rs1259197736, REVEL 0.66, ESM-1b 1.00
- R151K (p.Arg151Lys), rs2075720794, ClinGen CA413259505, ClinVar RCV001213339, Ensembl rs2075720794, ESM-1b 1.00, AlphaMissense 0.90, Likely benign, Congenital muscular hypertrophy-cerebral syndrome
- A153V (p.Ala153Val), rs1171109209, ClinGen CA413259490, ClinVar RCV001732506, ClinVar RCV002032718, REVEL 0.52, ESM-1b 1.00, Conflicting interpretations, Congenital muscular hypertrophy-cerebral syndrome; Developmental and epileptic e
- R160H (p.Arg160His), rs2075720699, ClinGen CA413259440, ClinVar RCV003394506, ClinVar RCV003624521, REVEL 0.62, ESM-1b 1.00, Uncertain significance, not provided; SMC1A-related disorder; Congenital muscular hypertrophy-cerebral s
- G162A (p.Gly162Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G162T (p.Gly162Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A165V (p.Ala165Val), rs1556890833, ClinGen CA413259409, ClinVar RCV000813864, ClinVar RCV002495143, REVEL 0.55, ESM-1b 1.00, Uncertain significance, Developmental and epileptic encephalopathy, 85, with or without midline brain de
- Q166R (p.Gln166Arg), rs2146605622, ClinGen CA413259404, ClinVar RCV002093946, Ensembl rs2146605622, ESM-1b 1.00, AlphaMissense 0.25, Benign, Congenital muscular hypertrophy-cerebral syndrome
- K170R (p.Lys170Arg), TOPMed rs1468174097, ESM-1b 0.00, AlphaMissense 0.06
- R171* (p.Arg171Ter), rs2520963220, ClinGen CA413259367, ClinVar RCV002470576, Pathogenic
- R171Q (p.Arg171Gln), rs2075720519, ClinGen CA413259364, cosmic curated COSV10522, ClinVar RCV001201950, REVEL 0.29, ESM-1b 0.97, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome
- K172R (p.Lys172Arg), gnomAD rs1556890827, REVEL 0.58, ESM-1b 1.00
- V176M (p.Val176Met), rs2520963158, ClinGen CA413259330, ClinVar RCV002690248, REVEL 0.28, ESM-1b 0.00, Uncertain significance, not provided; Congenital muscular hypertrophy-cerebral syndrome
- E180D (p.Glu180Asp), TOPMed rs1450248187, gnomAD rs1450248187, REVEL 0.41, ESM-1b 1.00
- Q183* (p.Gln183Ter), rs587784421, ClinGen CA272587, ClinVar RCV000147570, Ensembl rs587784421, Pathogenic
- F184L (p.Phe184Leu), Ensembl rs782669802, ESM-1b 1.00, AlphaMissense 1.00
- R188C (p.Arg188Cys), rs2146605558, ClinGen CA413259240, NCI-TCGA Cosmic COSV5913, cosmic curated COSV59131, ESM-1b 1.00, AlphaMissense 0.91, Uncertain significance, Inborn genetic diseases; Congenital muscular hypertrophy-cerebral syndrome
- E195* (p.Glu195Ter), rs1602413582, ClinGen CA413259192, ClinVar RCV000990835, Ensembl rs1602413582, Likely pathogenic
- R196C (p.Arg196Cys), rs587784422, ClinGen CA272592, NCI-TCGA Cosmic COSV5913, cosmic curated COSV59132, ESM-1b 1.00, AlphaMissense 0.99, Pathogenic, in CDLS2
- R196G (p.Arg196Gly), rs587784422, ClinGen CA413259184, ClinVar RCV001389992, Ensembl rs587784422, ESM-1b 1.00, AlphaMissense 0.99, Pathogenic, Congenital muscular hypertrophy-cerebral syndrome
- R196H (p.Arg196His), rs1556890815, ClinGen CA413259183, cosmic curated COSV59130, ClinVar RCV000639414, ESM-1b 1.00, AlphaMissense 0.98, Pathogenic, SMC1A-related disorder; Congenital muscular hypertrophy-cerebral syndrome
- A199T (p.Ala199Thr), rs2520962844, ClinGen CA413259157, ClinVar RCV003340884, ESM-1b 1.00, AlphaMissense 0.98, Uncertain significance, Developmental and epileptic encephalopathy, 85, with or without midline brain de
- E204V (p.Glu204Val), TOPMed rs1287375497, gnomAD rs1287375497, REVEL 0.61, ESM-1b 1.00
- R208G (p.Arg208Gly), rs1057520375, ClinGen CA16608889, ClinVar RCV000439297, ClinVar RCV001527652, ESM-1b 1.00, AlphaMissense 0.95, Pathogenic, not provided
- R208W (p.Arg208Trp), cosmic curated COSV59131, gnomAD rs1057520375, REVEL 0.80, ESM-1b 1.00, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome
- Q210* (p.Gln210Ter), rs2146605443, ClinGen CA413258994, ClinVar RCV001915104, Ensembl rs2146605443, Pathogenic
- Q210H (p.Gln210His), ExAC rs782027066, ESM-1b 1.00, AlphaMissense 0.79
- D214G (p.Asp214Gly), rs1001684337, ClinGen CA329907612, ClinVar RCV003051510, ClinVar RCV005744595, REVEL 0.71, ESM-1b 1.00, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome; not provided; Inborn genetic
- R218Q (p.Arg218Gln), rs2075719827, ClinGen CA413258909, ClinVar RCV002730105, ClinVar RCV005050629, REVEL 0.27, ESM-1b 0.45, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome; Developmental and epileptic e
- R218W (p.Arg218Trp), rs782811561, ClinGen CA10420647, ClinVar RCV002075129, ClinVar RCV005050535, REVEL 0.63, ESM-1b 1.00, Conflicting interpretations, Congenital muscular hypertrophy-cerebral syndrome; Developmental and epileptic e
- A219V (p.Ala219Val), Ensembl rs2075719793, REVEL 0.52, ESM-1b 0.17
- V221A (p.Val221Ala), cosmic curated COSV10962, gnomAD rs2075719772, REVEL 0.42, ESM-1b 1.00
- Q224* (p.Gln224Ter), gnomAD X-53380726-G-A, REVEL 0.73, MetaLR 0.54
- L228I (p.Leu228Ile), rs2520961952, ClinGen CA413258799, ClinVar RCV003397710, ESM-1b 1.00, AlphaMissense 0.68, Uncertain significance, SMC1A-related disorder
- H230Q (p.His230Gln), Ensembl rs972084651, ESM-1b 1.00, AlphaMissense 0.81
- H230R (p.His230Arg), ExAC rs782002189, gnomAD rs782002189, REVEL 0.86, ESM-1b 1.00
- E234K (p.Glu234Lys), Ensembl rs2075719646, ESM-1b 1.00, AlphaMissense 0.68
- L238R (p.Leu238Arg), Ensembl rs868916184, ESM-1b 1.00, AlphaMissense 0.66
- N239S (p.Asn239Ser), rs782172948, ClinGen CA10420644, ClinVar RCV001986144, ClinVar RCV003448444, REVEL 0.24, ESM-1b 1.00, Uncertain significance, Developmental and epileptic encephalopathy, 85, with or without midline brain de
- K240E (p.Lys240Glu), ExAC rs781938358, gnomAD rs781938358, REVEL 0.26, ESM-1b 0.00
- S244L (p.Ser244Leu), Ensembl rs2075719521, REVEL 0.24, ESM-1b 0.19
- S244N (p.Ser244Asn), gnomAD X-53380707-C-T, ESM-1b 0.00, AlphaMissense 0.09
- N246K (p.Asn246Lys), rs2520961607, ClinGen CA413258608, ClinVar RCV002572493, ESM-1b 1.00, AlphaMissense 0.57, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome
- K247E (p.Lys247Glu), rs2075719463, ClinGen CA413258606, ClinVar RCV003625729, Ensembl rs2075719463, REVEL 0.23, ESM-1b 1.00, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome
- E248Q (p.Glu248Gln), gnomAD rs1556890765, ESM-1b 1.00, AlphaMissense 0.19
- D252E (p.Asp252Glu), rs370671274, ClinGen CA413258561, ClinVar RCV001270902, ESP rs370671274, REVEL 0.21, ESM-1b 0.00, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome
- D252V (p.Asp252Val), gnomAD rs1556890763, REVEL 0.33, ESM-1b 0.82
- R255C (p.Arg255Cys), rs782209409, ClinGen CA10420638, cosmic curated COSV10815, ClinVar RCV001320460, REVEL 0.64, ESM-1b 1.00, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome
- R255H (p.Arg255His), rs782606119, ClinGen CA10420637, ClinVar RCV001034190, ClinVar RCV003314659, REVEL 0.40, ESM-1b 1.00, Conflicting interpretations, not provided; Congenital muscular hypertrophy-cerebral syndrome
- R255L (p.Arg255Leu), ExAC rs782606119, TOPMed rs782606119, gnomAD rs782606119, REVEL 0.36, ESM-1b 1.00, Likely benign
- R255P (p.Arg255Pro), rs782606119, ClinGen CA413258539, ClinVar RCV003513087, ClinVar RCV004780575, ESM-1b 1.00, AlphaMissense 0.23, Uncertain significance, not provided; Congenital muscular hypertrophy-cerebral syndrome
- R255K (p.Arg255Lys), rs138015913, gnomAD X-53380668-C-T, ESM-1b 0.00, AlphaMissense 0.10
- R255Q (p.Arg255Gln), rs782763816, gnomAD X-53380704-C-T, ESM-1b 1.00, AlphaMissense 0.13
- K258R (p.Lys258Arg), rs897112776, ClinGen CA329907610, ClinVar RCV003624864, TOPMed rs897112776, REVEL 0.26, ESM-1b 0.70, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome
- L263P (p.Leu263Pro), gnomAD X-53380674-A-G, ESM-1b 1.00, AlphaMissense 1.00
- K267R (p.Lys267Arg), rs2520961160, ClinGen CA413258396, ClinVar RCV003624818, REVEL 0.39, ESM-1b 1.00, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome
- K268E (p.Lys268Glu), rs1569359008, ClinGen CA413258385, ClinVar RCV002255033, Ensembl rs1569359008, REVEL 0.60, ESM-1b 1.00, Likely benign, not provided
- L270P (p.Leu270Pro), gnomAD X-53380623-A-G, ESM-1b 1.00, AlphaMissense 1.00
- L270S (p.Leu270Ser), gnomAD X-53380635-A-G, ESM-1b 0.99, AlphaMissense 0.83
- G271T (p.Gly271Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- G271D (p.Gly271Asp), rs2146605306, ClinGen CA413258347, ClinVar RCV001963542, Ensembl rs2146605306, ESM-1b 1.00, AlphaMissense 1.00, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome
- R275Q (p.Arg275Gln), rs2520960966, ClinGen CA413258298, ClinVar RCV003624531, ClinVar RCV004765918, REVEL 0.79, ESM-1b 1.00, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome; not provided
- R275W (p.Arg275Trp), rs781812690, ClinGen CA10420635, ClinVar RCV002009121, ClinVar RCV005925503, REVEL 0.74, ESM-1b 1.00, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome
- R275K (p.Arg275Lys), gnomAD X-53380644-C-T, ESM-1b 1.00, AlphaMissense 0.76
- E276D (p.Glu276Asp), Ensembl rs2075718827, ESM-1b 0.00, AlphaMissense 0.16
- I280T (p.Ile280Thr), rs1569351427, gnomAD X-53380626-A-G, ESM-1b 1.00, AlphaMissense 0.29
- S289Y (p.Ser289Tyr), gnomAD X-53380629-G-T, ESM-1b 0.87, AlphaMissense 0.56
- S289* (p.Ser289Ter), gnomAD X-53380638-G-T, CADD 8.62
- S289L (p.Ser289Leu), gnomAD X-53380638-G-A, ESM-1b 0.00, AlphaMissense 0.18
- K294N (p.Lys294Asn), TOPMed rs1197410298, gnomAD rs1197410298, REVEL 0.60, ESM-1b 1.00
- P296S (p.Pro296Ser), TOPMed rs2075715503, ESM-1b 1.00, AlphaMissense 0.99
- P296L (p.Pro296Leu), rs146216425, gnomAD X-53380647-G-A, ESM-1b 1.00, AlphaMissense 0.99
- P296R (p.Pro296Arg), rs146216425, gnomAD X-53380647-G-C, ESM-1b 1.00, AlphaMissense 1.00
- E303D (p.Glu303Asp), rs2520958047, ClinGen CA413257927, ClinVar RCV003511636, ESM-1b 1.00, AlphaMissense 1.00, Pathogenic, Congenital muscular hypertrophy-cerebral syndrome
- N304K (p.Asn304Lys), ExAC rs782636844, gnomAD rs782636844, ESM-1b 1.00, AlphaMissense 0.89
- T305I (p.Thr305Ile), rs2075578868, gnomAD X-53380656-G-A, ESM-1b 1.00, AlphaMissense 0.89
- S306Y (p.Ser306Tyr), rs2146604807, ClinGen CA413257890, ClinVar RCV001977137, Ensembl rs2146604807, ESM-1b 1.00, AlphaMissense 0.79, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome
- H307R (p.His307Arg), rs1556890616, ClinGen CA413257876, ClinVar RCV000556180, Ensembl rs1556890616, ESM-1b 1.00, AlphaMissense 0.98, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome
- E313K (p.Glu313Lys), rs2520957938, ClinGen CA413257801, ClinVar RCV003022887, ClinVar RCV005241514, ESM-1b 1.00, AlphaMissense 0.84, Conflicting interpretations, Congenital muscular hypertrophy-cerebral syndrome; not provided
- A314T (p.Ala314Thr), gnomAD rs2075715405, REVEL 0.20, ESM-1b 1.00
- A315V (p.Ala315Val), gnomAD rs1556890615, ESM-1b 1.00, AlphaMissense 0.76
- K316R (p.Lys316Arg), rs1377540307, ClinGen CA413257755, ClinVar RCV002604572, TOPMed rs1377540307, REVEL 0.24, ESM-1b 1.00, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome
- L319A (p.Leu319Ala), rs2520957861, ClinGen CA2739273514, ClinVar RCV003625286, ESM-1b 0.85, AlphaMissense 0.68, Pathogenic
- Q323R (p.Gln323Arg), Ensembl rs1602413015, ESM-1b 1.00, AlphaMissense 0.13
- K324E (p.Lys324Glu), rs2520957778, ClinGen CA413257657, ClinVar RCV002303215, ESM-1b 1.00, AlphaMissense 0.56, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome
- Y326F (p.Tyr326Phe), rs2520957741, ClinGen CA413257618, ClinVar RCV002837674, ESM-1b 0.64, AlphaMissense 0.09, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome
- R329H (p.Arg329His), rs782449052, ClinGen CA10420614, cosmic curated COSV59129, ClinVar RCV002077487, REVEL 0.27, ESM-1b 1.00, Likely benign, Congenital muscular hypertrophy-cerebral syndrome
- R329L (p.Arg329Leu), rs782449052, ClinGen CA413257570, ClinVar RCV001771335, ExAC rs782449052, ESM-1b 1.00, AlphaMissense 1.00, Uncertain significance, not provided
- R329P (p.Arg329Pro), rs782449052, ClinGen CA413257573, ClinVar RCV002036925, ExAC rs782449052, ESM-1b 1.00, AlphaMissense 1.00, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome
- K330N (p.Lys330Asn), Ensembl rs1172651579, ESM-1b 1.00, AlphaMissense 0.60
- E335D (p.Glu335Asp), rs2520957574, ClinGen CA413257482, ClinVar RCV003625889, ESM-1b 0.00, AlphaMissense 0.18, Benign, Congenital muscular hypertrophy-cerebral syndrome
- K338N (p.Lys338Asn), rs893697991, ClinGen CA329907584, ClinVar RCV002842100, TOPMed rs893697991, REVEL 0.24, ESM-1b 1.00, Conflicting interpretations, not provided; not specified; Congenital muscular hypertrophy-cerebral syndrome
- E339K (p.Glu339Lys), gnomAD rs1556890600, ESM-1b 1.00, AlphaMissense 0.92
- E344Q (p.Glu344Gln), ESP rs375853850, ExAC rs375853850, TOPMed rs375853850, gnomAD rs375853850, REVEL 0.53, ESM-1b 1.00
- A346G (p.Ala346Gly), NCI-TCGA Cosmic COSV1004, cosmic curated COSV10044, Variant assessed as somatic; moderate impact.
- A346S (p.Ala346Ser), ExAC rs782111343, TOPMed rs782111343, gnomAD rs782111343, REVEL 0.24, ESM-1b 0.65
- Q348R (p.Gln348Arg), gnomAD rs1556890595, REVEL 0.28, ESM-1b 0.00
- E349G (p.Glu349Gly), gnomAD rs1556890594, ESM-1b 1.00, AlphaMissense 0.28
- F350V (p.Phe350Val), gnomAD rs1556890589, ESM-1b 1.00, AlphaMissense 0.95
- R353Q (p.Arg353Gln), cosmic curated COSV10737, 1000Genomes rs2146604742, REVEL 0.23, ESM-1b 0.00
- R353W (p.Arg353Trp), rs781862992, ClinGen CA10420610, NCI-TCGA Cosmic COSV5912, cosmic curated COSV59127, REVEL 0.47, ESM-1b 1.00, Conflicting interpretations, Developmental and epileptic encephalopathy, 85, with or without midline brain de
- G362A (p.Gly362Ala), NCI-TCGA Cosmic COSV5912, cosmic curated COSV59127, Variant assessed as somatic; moderate impact.
- G362S (p.Gly362Ser), rs2520957067, ClinGen CA413257112, ClinVar RCV003129454, ESM-1b 1.00, AlphaMissense 0.94, Uncertain significance, not provided
- T366M (p.Thr366Met), Ensembl rs937651485, REVEL 0.30, ESM-1b 1.00
- E368K (p.Glu368Lys), rs2146604722, ClinGen CA413257031, ClinVar RCV002226866, Ensembl rs2146604722, ESM-1b 1.00, AlphaMissense 0.82, Likely pathogenic, Congenital muscular hypertrophy-cerebral syndrome
- N370S (p.Asn370Ser), gnomAD rs1556890585, REVEL 0.23, ESM-1b 0.00
- K373R (p.Lys373Arg), rs2146604633, ClinGen CA413256947, ClinVar RCV002273160, Ensembl rs2146604633, ESM-1b 0.38, AlphaMissense 0.11, Uncertain significance, Developmental and epileptic encephalopathy, 85, with or without midline brain de
- R377Q (p.Arg377Gln), rs782541938, ClinGen CA10420596, ClinVar RCV003091265, ClinVar RCV005045270, REVEL 0.10, ESM-1b 0.00, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome; Developmental and epileptic e
- A382G (p.Ala382Gly), rs2520969362, ClinGen CA413131501, ClinVar RCV003242359, ClinVar RCV006262760, Uncertain significance
- S383R (p.Ser383Arg), rs2520956183, ClinGen CA413256796, ClinVar RCV003625429, REVEL 0.21, ESM-1b 1.00, Uncertain significance, Congenital muscular hypertrophy-cerebral syndrome
- K384E (p.Lys384Glu), rs2075714342, ClinGen CA413256795, ClinVar RCV001195912, Ensembl rs2075714342, ESM-1b 1.00, AlphaMissense 0.94, Uncertain significance, Developmental and epileptic encephalopathy, 85, with or without midline brain de
- A386G (p.Ala386Gly), ExAC rs782473597, gnomAD rs782473597, REVEL 0.15, ESM-1b 1.00
- Q391* (p.Gln391Ter), rs2146604602, ClinGen CA413256701, ClinVar RCV001788517, ClinVar RCV004591536, Pathogenic
- N397I (p.Asn397Ile), ExAC rs782697006, TOPMed rs782697006, REVEL 0.60, ESM-1b 1.00, Uncertain significance
- N397S (p.Asn397Ser), rs782697006, ClinGen CA10420591, ClinVar RCV000499405, ClinVar RCV000704265, REVEL 0.41, ESM-1b 1.00, Uncertain significance, Inborn genetic diseases; Congenital muscular hypertrophy-cerebral syndrome; not
- R398* (p.Arg398Ter), rs886041902, ClinGen CA10603610, ClinVar RCV000342065, Ensembl rs886041902, CADD 32.00, Pathogenic, in CDLS2
- R398G (p.Arg398Gly), UniProt VAR 078274, ESM-1b 1.00, AlphaMissense 0.98, Pathogenic, in CDLS2
Public SMC1A analysis runs
- SMC1A analysis run — SMC1A (782 variants) — completed 2026-10-09