CBS (Cystathionine beta-synthase) variants and mutations
CBS (also known as Cystathionine beta-synthase) is a human protein-coding gene encoding a cystathionine beta-synthase protein. A vitamin B6-dependent enzyme that combines homocysteine and serine to form cystathionine in the transsulfuration pathway. Deficiency causes homocystinuria. This analysis covers 1,002 CBS variants and mutations. Of these, 97% have computational variant effect predictions. Disease context includes classic homocystinuria, homocystinuria, and hyperhomocysteinemia, thrombotic, cbs-related. Example CBS variants include M1T, P2L, and E4D.
Variant analysis overview
- Gene: CBS
- Protein: Cystathionine beta-synthase
- UniProt accession: P35520
- Organism: Homo sapiens
- Variants analyzed: 1002
- Variant scope: all variants
- Completed: 2026-10-09
Variant and mutation evidence
- Variant composition: 736 unspecified-consequence records; 5 stop lost; 60 synonymous variants; 167 missense variants; 11 frameshift variants; 10 stop-gained variants; 1 in-frame insertions; 3 in-frame deletions; 6 splice-region variants; 10 substitution
- Prediction scores: 968 variants have prediction scores (97% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: classic homocystinuria, homocystinuria, hyperhomocysteinemia, thrombotic, cbs-related, familial thoracic aortic aneurysm and aortic dissection, Marfan syndrome, connective tissue disorder, hyperhomocysteinemia, Abnormality of metabolism/homeostasis, Abnormality of the cardiovascular system, Intellectual disability, supranuclear palsy, progressive, 1, neoplasm.
Protein structure and variant hotspots
- Protein features: 1 domains; 5 binding sites; 3 post-translational modification sites.
- Structural context: 73 variants have structural context.
- PTM context: 11 variants overlap post-translational modification sites.
- Experimental data: 550 protein positions have experimental scores. Source: CBS low-B6 imputed and refined, CBS low-B6, CBS high-B6.
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 CBS
- Familial thoracic aortic aneurysm and aortic dissection genes and variants
- Hyperhomocysteinemia, thrombotic, cbs-related genes and variants
- Homocystinuria genes and variants
- Classic homocystinuria genes and variants
- Connective tissue disease genes and variants
- Thoracic aortic aneurysm or dissection genes and variants
Notable CBS variants
Examples include M1T, P2L, E4D, T5A, T5N, P6S, P6T, Q7E. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1T (p.Met1Thr), rs769766030, ClinGen CA243089, ClinVar RCV000176975, ClinVar RCV003597965, ESM-1b 1.00, AlphaMissense 0.49, Conflicting interpretations, not provided; HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
- P2L (p.Pro2Leu), rs546530618, ClinGen CA324871, ClinVar RCV002291590, ClinVar RCV002354543, ESM-1b 0.00, AlphaMissense 0.13, Uncertain significance, not provided; Familial thoracic aortic aneurysm and aortic dissection; HYPERHOMO
- E4D (p.Glu4Asp), ExAC rs748832676, ESM-1b 0.00, AlphaMissense 0.08
- T5A (p.Thr5Ala), rs2146429088, ClinGen CA410602621, ClinVar RCV001950186, ClinVar RCV005241478, ESM-1b 0.00, AlphaMissense 0.07, Uncertain significance, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED; not provided
- T5N (p.Thr5Asn), rs2517484287, ClinGen CA410602619, ClinVar RCV003093071, ESM-1b 0.00, AlphaMissense 0.07, Uncertain significance, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
- P6S (p.Pro6Ser), 1000Genomes rs528184368, ExAC rs528184368, gnomAD rs528184368, ESM-1b 0.00, AlphaMissense 0.07
- P6T (p.Pro6Thr), cosmic curated COSV10742, ESM-1b 0.00, AlphaMissense 0.06
- Q7E (p.Gln7Glu), cosmic curated COSV10647, ESM-1b 0.00, AlphaMissense 0.06
- A8G (p.Ala8Gly), rs919403971, ClinGen CA321104173, ClinVar RCV003078656, ClinVar RCV003294482, ESM-1b 0.00, AlphaMissense 0.08, Uncertain significance, not specified; HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED; Familial thoracic
- A8V (p.Ala8Val), rs919403971, ClinGen CA410602599, ClinVar RCV002242412, ClinVar RCV003169729, ESM-1b 0.00, AlphaMissense 0.08, Uncertain significance, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED; Familial thoracic aortic aneurysm
- E9K (p.Glu9Lys), ExAC rs758092887, gnomAD rs758092887, ESM-1b 0.00, AlphaMissense 0.07
- E9Q (p.Glu9Gln), ExAC rs758092887, gnomAD rs758092887, ESM-1b 0.00, AlphaMissense 0.08
- V10L (p.Val10Leu), rs1479837105, ClinGen CA410602589, ClinVar RCV002766723, ESM-1b 0.00, AlphaMissense 0.09, Uncertain significance, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
- V10M (p.Val10Met), gnomAD rs1479837105, ESM-1b 0.00, AlphaMissense 0.09, Uncertain significance, Classic homocystinuria
- G11R (p.Gly11Arg), gnomAD rs1205411379, ESM-1b 0.00, AlphaMissense 0.09, Uncertain significance, Homocystinuria; Classic homocystinuria; HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RE
- P12S (p.Pro12Ser), rs558259739, ClinGen CA321523, ClinVar RCV002229439, ClinVar RCV002336521, ESM-1b 0.00, AlphaMissense 0.06, Conflicting interpretations, Familial thoracic aortic aneurysm and aortic dissection; not provided; HYPERHOMO
- G14V (p.Gly14Val), gnomAD rs1371674515, ESM-1b 0.00, AlphaMissense 0.08
- C15F (p.Cys15Phe), ExAC rs750850447, gnomAD rs750850447, ESM-1b 0.00, AlphaMissense 0.11
- P16L (p.Pro16Leu), cosmic curated COSV10888, ESM-1b 0.00, AlphaMissense 0.09
- H17L (p.His17Leu), ExAC rs768172160, ESM-1b 0.00, AlphaMissense 0.08
- H17N (p.His17Asn), rs2146428735, ClinGen CA410602549, ClinVar RCV001929731, Ensembl rs2146428735, ESM-1b 0.00, AlphaMissense 0.11, Uncertain significance, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
- R18C (p.Arg18Cys), rs201827340, ClinGen CA10587951, cosmic curated COSV61443, ClinVar RCV000359251, ESM-1b 0.00, AlphaMissense 0.11, Benign/Likely benign, not specified; not provided; Familial thoracic aortic aneurysm and aortic dissec
- R18H (p.Arg18His), cosmic curated COSV61441, gnomAD rs755850396, ESM-1b 0.00, AlphaMissense 0.07
- R18S (p.Arg18Ser), rs201827340, ClinGen CA321104102, cosmic curated COSV61446, ClinVar RCV002241272, ESM-1b 0.00, AlphaMissense 0.11, Uncertain significance, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
- S19L (p.Ser19Leu), rs764399291, ClinGen CA321104095, ClinVar RCV002982353, ExAC rs764399291, ESM-1b 0.00, AlphaMissense 0.08, Uncertain significance, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
- G20E (p.Gly20Glu), rs1983457688, ClinGen CA410602531, cosmic curated COSV61442, ClinVar RCV002240956, ESM-1b 0.00, AlphaMissense 0.08, Uncertain significance, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED; Familial thoracic aortic aneurysm
- H22L (p.His22Leu), cosmic curated COSV10647, ESM-1b 0.00, AlphaMissense 0.06
- H22R (p.His22Arg), rs763151207, ClinGen CA321891, ClinVar RCV000197426, ClinVar RCV000648122, ESM-1b 0.00, AlphaMissense 0.06, Uncertain significance, not specified; not provided; Familial thoracic aortic aneurysm and aortic dissec
- S23L (p.Ser23Leu), rs775785018, ClinGen CA321104075, ClinVar RCV000798452, ClinVar RCV001538815, ESM-1b 0.00, AlphaMissense 0.07, Conflicting interpretations, not provided; HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED; Familial thoracic a
- S23T (p.Ser23Thr), gnomAD rs1378750597, ESM-1b 0.00, AlphaMissense 0.07
- A24V (p.Ala24Val), rs759682004, ClinGen CA321104045, cosmic curated COSV61441, ClinVar RCV001091466, ESM-1b 0.00, AlphaMissense 0.08, Uncertain significance, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED; not provided; Familial thoracic a
- K25E (p.Lys25Glu), cosmic curated COSV61442, ESM-1b 0.00, AlphaMissense 0.07
- K25N (p.Lys25Asn), rs1484147890, ClinGen CA410602498, cosmic curated COSV61443, ClinVar RCV001896245, ESM-1b 0.00, AlphaMissense 0.12, Uncertain significance, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED; Familial thoracic aortic aneurysm
- G26A (p.Gly26Ala), rs746782366, ClinGen CA321104037, ClinVar RCV002409910, ClinVar RCV004782930, ESM-1b 0.00, AlphaMissense 0.08, Uncertain significance, not specified; not provided; Familial thoracic aortic aneurysm and aortic dissec
- G26E (p.Gly26Glu), cosmic curated COSV61442, ExAC rs746782366, gnomAD rs746782366, ESM-1b 0.00, AlphaMissense 0.07, Uncertain significance
- S27I (p.Ser27Ile), ExAC rs771748290, gnomAD rs771748290, ESM-1b 0.00, AlphaMissense 0.07
- S27N (p.Ser27Asn), ExAC rs771748290, gnomAD rs771748290, ESM-1b 0.00, AlphaMissense 0.07
- S27R (p.Ser27Arg), 1000Genomes rs530296903, ExAC rs530296903, gnomAD rs530296903, ESM-1b 0.00, AlphaMissense 0.12
- E29K (p.Glu29Lys), ExAC rs778653743, ESM-1b 0.00, AlphaMissense 0.08
- G31E (p.Gly31Glu), rs1226779462, ClinGen CA410602464, ClinVar RCV004118816, gnomAD rs1226779462, ESM-1b 0.00, AlphaMissense 0.06, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- S32P (p.Ser32Pro), ExAC rs753430439, gnomAD rs753430439, ESM-1b 0.00, AlphaMissense 0.05, Likely benign, Familial thoracic aortic aneurysm and aortic dissection
- P33S (p.Pro33Ser), 1000Genomes rs563211474, ExAC rs563211474, gnomAD rs563211474, ESM-1b 0.00, AlphaMissense 0.07, Uncertain significance, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED; not provided; Familial thoracic a
- E34G (p.Glu34Gly), ExAC rs757899237, gnomAD rs757899237, ESM-1b 0.00, AlphaMissense 0.05
- D35N (p.Asp35Asn), rs368471318, ClinGen CA410602444, ClinVar RCV003112258, ESP rs368471318, ESM-1b 0.00, AlphaMissense 0.08, Uncertain significance, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
- D35Y (p.Asp35Tyr), rs368471318, ClinGen CA321103959, ClinVar RCV002389708, ClinVar RCV003095232, ESM-1b 0.08, AlphaMissense 0.08, Uncertain significance, CBS-related disorder; Cardiovascular phenotype; Familial thoracic aortic aneurys
- K36E (p.Lys36Glu), rs904453895, ClinGen CA321103958, ClinVar RCV001855274, ClinVar RCV002314210, ESM-1b 0.00, AlphaMissense 0.06, Uncertain significance, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED; Familial thoracic aortic aneurysm
- A38P (p.Ala38Pro), gnomAD rs1064795253, ESM-1b 0.00, AlphaMissense 0.08, Uncertain significance
- A38T (p.Ala38Thr), rs1064795253, ClinGen CA16621018, ClinVar RCV000483422, gnomAD rs1064795253, ESM-1b 0.00, AlphaMissense 0.08, Uncertain significance, not provided
- E40D (p.Glu40Asp), ExAC rs764487170, gnomAD rs764487170, ESM-1b 0.00, AlphaMissense 0.08, Uncertain significance, CBS-related disorder; Familial thoracic aortic aneurysm and aortic dissection
- P41L (p.Pro41Leu), gnomAD rs1315746924, ESM-1b 0.00, AlphaMissense 0.06, Uncertain significance, Classic homocystinuria
- P41S (p.Pro41Ser), ExAC rs763389870, gnomAD rs763389870, ESM-1b 0.00, AlphaMissense 0.08
- W43* (p.Trp43Ter), cosmic curated COSV61443, cosmic curated COSV61442
- W43C (p.Trp43Cys), gnomAD rs1375321603, ESM-1b 0.00, AlphaMissense 0.75, Uncertain significance, not provided
- W43R (p.Trp43Arg), cosmic curated COSV61442, ESM-1b 0.00, AlphaMissense 0.80
- I44M (p.Ile44Met), rs1334019279, ClinGen CA410602377, ClinVar RCV002385881, gnomAD rs1334019279, ESM-1b 0.00, AlphaMissense 0.12, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- R45Q (p.Arg45Gln), rs759502207, ClinGen CA10583892, ClinVar RCV000229516, ClinVar RCV001658051, ESM-1b 0.00, AlphaMissense 0.13, Uncertain significance, not specified; not provided; Familial thoracic aortic aneurysm and aortic dissec
- R45W (p.Arg45Trp), rs201372812, ClinGen CA323483, cosmic curated COSV61445, ClinVar RCV000198945, ESM-1b 0.76, AlphaMissense 0.15, Conflicting interpretations, not specified; not provided; Familial thoracic aortic aneurysm and aortic dissec
- D47A (p.Asp47Ala), rs2146427913, ClinGen CA410602362, ClinVar RCV002006214, Ensembl rs2146427913, ESM-1b 0.00, AlphaMissense 0.46, Likely pathogenic, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
- D47N (p.Asp47Asn), rs2517483238, ClinGen CA410602367, ClinVar RCV002730976, ESM-1b 0.00, AlphaMissense 0.20, Likely pathogenic, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
- P49L (p.Pro49Leu), rs148865119, ClinGen CA325105, cosmic curated COSV10526, ClinVar RCV000200523, ESM-1b 0.00, AlphaMissense 0.10, Pathogenic/Likely pathogenic, CBS-related disorder; Autosomal recessive CBS-related disorders; Homocystinuria
- P49R (p.Pro49Arg), ESP rs148865119, ExAC rs148865119, gnomAD rs148865119, ESM-1b 0.00, AlphaMissense 0.08, Pathogenic, in CBSD
- P49S (p.Pro49Ser), cosmic curated COSV61445, ESM-1b 0.00, AlphaMissense 0.10
- S50N (p.Ser50Asn), rs2517483166, ClinGen CA410602346, ClinVar RCV004356092, ESM-1b 0.00, AlphaMissense 0.39, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- R51K (p.Arg51Lys), rs370983323, ClinGen CA16621017, cosmic curated COSV61444, ClinVar RCV000486724, ESM-1b 0.00, AlphaMissense 0.08, Uncertain significance, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED; not provided; Familial thoracic a
- R51S (p.Arg51Ser), rs748795053, ClinGen CA410602336, ClinVar RCV002403148, ClinVar RCV005648220, ESM-1b 0.00, AlphaMissense 0.30, Uncertain significance, not provided; Familial thoracic aortic aneurysm and aortic dissection
- C52* (p.Cys52Ter), rs1983442077, ClinGen CA410602330, ClinVar RCV002240573, Ensembl rs1983442077, Pathogenic
- C52S (p.Cys52Ser), rs2146427772, ClinGen CA410602335, ClinVar RCV002042352, Ensembl rs2146427772, ESM-1b 0.00, AlphaMissense 0.94, Likely pathogenic, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
- C52Y (p.Cys52Tyr), rs779777933, ClinGen CA321103843, ClinVar RCV002235502, ClinVar RCV004771484, ESM-1b 0.00, AlphaMissense 0.89, Uncertain significance, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED; Classic homocystinuria
- T53I (p.Thr53Ile), Ensembl rs564501381, ESM-1b 0.00, AlphaMissense 0.13
- W54* (p.Trp54Ter), rs199948079, ClinGen CA321707, ClinVar RCV000409663, ClinVar RCV002229029, Pathogenic
- Q55K (p.Gln55Lys), gnomAD rs1292304665, ESM-1b 0.00, AlphaMissense 0.07
- L56P (p.Leu56Pro), gnomAD rs1180472259, ESM-1b 0.00, AlphaMissense 0.06
- G57D (p.Gly57Asp), rs1295461215, ClinGen CA410602299, ClinVar RCV001813042, ClinVar RCV001830087, ESM-1b 0.00, AlphaMissense 0.15, Uncertain significance, not provided
- G57S (p.Gly57Ser), gnomAD rs1480938544, ESM-1b 0.00, AlphaMissense 0.11
- R58L (p.Arg58Leu), cosmic curated COSV10967, ESM-1b 0.00, AlphaMissense 0.08
- R58Q (p.Arg58Gln), cosmic curated COSV10967, ExAC rs758648251, gnomAD rs758648251, ESM-1b 0.00, AlphaMissense 0.07, Uncertain significance, not provided
- R58W (p.Arg58Trp), rs555959266, ClinGen CA321103816, ClinVar RCV001963724, UniProt VAR 008050, ESM-1b 0.53, AlphaMissense 0.10, Uncertain significance, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
- P59S (p.Pro59Ser), rs376496085, ClinGen CA321103799, ClinVar RCV002241156, ClinVar RCV002402692, ESM-1b 0.00, AlphaMissense 0.08, Conflicting interpretations, not specified; not provided; HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
- A60V (p.Ala60Val), rs765352771, ClinGen CA321103781, ClinVar RCV001317527, ClinVar RCV002241981, ESM-1b 0.00, AlphaMissense 0.07, Uncertain significance, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
- S61C (p.Ser61Cys), cosmic curated COSV10065, ESM-1b 0.00, AlphaMissense 0.09
- S61P (p.Ser61Pro), cosmic curated COSV10888, gnomAD rs1392721766, ESM-1b 0.00, AlphaMissense 0.08
- E62K (p.Glu62Lys), rs199507134, ClinGen CA321103764, ClinVar RCV002937689, ClinVar RCV005227802, ESM-1b 0.00, AlphaMissense 0.08, Uncertain significance, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED; not provided; Familial thoracic a
- P64A (p.Pro64Ala), Ensembl rs1983434122, ESM-1b 0.00, AlphaMissense 0.15
- H65L (p.His65Leu), rs1191141364, ClinGen CA410602252, ClinVar RCV003597752, ESM-1b 0.00, AlphaMissense 0.55, Likely pathogenic, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
- H65R (p.His65Arg), rs1191141364, ClinGen CA410602253, ClinVar RCV001981105, ClinVar RCV004770355, ESM-1b 0.00, AlphaMissense 0.55, Pathogenic, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED; not provided
- H67Y (p.His67Tyr), gnomAD rs1248573959, ESM-1b 0.04, AlphaMissense 0.10
- T68A (p.Thr68Ala), rs2517482628, ClinGen CA410602231, ClinVar RCV002419752, ESM-1b 0.00, AlphaMissense 0.05, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- T68I (p.Thr68Ile), ExAC rs760770298, gnomAD rs760770298, ESM-1b 0.03, AlphaMissense 0.07, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- A69P (p.Ala69Pro), rs17849313, UniProt VAR 046922, Ensembl rs17849313, ESM-1b 0.00, AlphaMissense 0.07
- P70L (p.Pro70Leu), rs2229413, ClinGen CA323808, cosmic curated COSV61444, ClinVar RCV000199276, ESM-1b 0.47, AlphaMissense 0.06, Conflicting interpretations, not specified; Familial thoracic aortic aneurysm and aortic dissection; HYPERHOM
- P70R (p.Pro70Arg), rs2229413, ClinGen CA321103742, ClinVar RCV002472146, ClinVar RCV002573625, ESM-1b 0.29, AlphaMissense 0.06, Uncertain significance, Classic homocystinuria; HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED; Familial
- A71E (p.Ala71Glu), cosmic curated COSV61444, ExAC rs761878715, gnomAD rs761878715, REVEL 0.38, ESM-1b 0.00
- A71V (p.Ala71Val), ExAC rs761878715, gnomAD rs761878715, REVEL 0.34, ESM-1b 0.00
- K72I (p.Lys72Ile), rs192232907, ClinGen CA320825, cosmic curated COSV10065, ClinVar RCV000196407, REVEL 0.36, ESM-1b 0.48, Conflicting interpretations, Connective tissue disorder; not specified; not provided
- K72N (p.Lys72Asn), Ensembl rs1983118913, REVEL 0.22, ESM-1b 0.00, Uncertain significance, not provided
- S73C (p.Ser73Cys), rs2517470142, ClinGen CA2580099043, ClinVar RCV002307179, REVEL 0.33, ESM-1b 1.00, Uncertain significance, not specified
- P74L (p.Pro74Leu), rs762862715, ClinGen CA321100449, cosmic curated COSV10888, ClinVar RCV001248604, REVEL 0.37, ESM-1b 1.00, Uncertain significance, not specified; Familial thoracic aortic aneurysm and aortic dissection; HYPERHOM
- P74S (p.Pro74Ser), gnomAD rs1170538361, REVEL 0.38, ESM-1b 0.00
- K75N (p.Lys75Asn), 1000Genomes rs552179536, ExAC rs552179536, gnomAD rs552179536, REVEL 0.36, ESM-1b 1.00, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- I76V (p.Ile76Val), Ensembl rs1601375965, ESM-1b 0.00, AlphaMissense 0.11
- P78R (p.Pro78Arg), rs786204608, ClinGen CA274218, ClinVar RCV000169367, ClinVar RCV002444679, REVEL 0.95, ESM-1b 1.00, Uncertain significance, not specified
- I80V (p.Ile80Val), ExAC rs769608918, gnomAD rs769608918, REVEL 0.56, ESM-1b 0.00
- L81V (p.Leu81Val), rs1480481730, ClinGen CA410602142, ClinVar RCV003324458, ClinVar RCV004823146, ESM-1b 0.49, AlphaMissense 0.19, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; not specified
- K82E (p.Lys82Glu), gnomAD rs1983113767, REVEL 0.33, ESM-1b 0.00
- K82N (p.Lys82Asn), ExAC rs71322504, gnomAD rs71322504, REVEL 0.22, ESM-1b 0.00
- I84T (p.Ile84Thr), rs2517469935, ClinGen CA410602121, ClinVar RCV003306666, ESM-1b 1.00, AlphaMissense 0.18, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- G85E (p.Gly85Glu), TOPMed rs1983111471, REVEL 0.93, ESM-1b 1.00
- G85R (p.Gly85Arg), rs863223435, ClinGen CA319849, cosmic curated COSV61446, ClinVar RCV000195506, REVEL 0.94, ESM-1b 1.00, Pathogenic, not provided; Classic homocystinuria; HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELA
- G85W (p.Gly85Trp), gnomAD rs863223435, REVEL 0.92, ESM-1b 1.00, Pathogenic, in CBSD
- D86G (p.Asp86Gly), cosmic curated COSV61443, REVEL 0.38, ESM-1b 0.54
- D86N (p.Asp86Asn), ExAC rs776259258, gnomAD rs776259258, REVEL 0.24, ESM-1b 0.00
- T87I (p.Thr87Ile), rs1239864776, ClinGen CA410602100, ClinVar RCV003172294, gnomAD rs1239864776, REVEL 0.97, ESM-1b 1.00, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- T87N (p.Thr87Asn), UniProt VAR 074590, REVEL 0.93, ESM-1b 1.00, Pathogenic, in CBSD
- P88A (p.Pro88Ala), rs2146413970, ClinGen CA410602098, ClinVar RCV002601595, ClinVar RCV003340518, ESM-1b 1.00, AlphaMissense 0.75, Conflicting interpretations, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED; Classic homocystinuria
- P88L (p.Pro88Leu), NCI-TCGA Cosmic COSV6144, cosmic curated COSV61442, REVEL 0.96, ESM-1b 1.00, Variant assessed as somatic; moderate impact., in CBSD
- P88R (p.Pro88Arg), rs2517469721, ClinGen CA410602095, ClinVar RCV003496394, ESM-1b 1.00, AlphaMissense 0.83, Likely pathogenic, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
- P88S (p.Pro88Ser), rs2146413970, ClinGen CA410602097, cosmic curated COSV10466, ClinVar RCV002242808, ESM-1b 1.00, AlphaMissense 0.75, Pathogenic/Likely pathogenic, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED; Classic homocystinuria
- M89I (p.Met89Ile), ExAC rs748617584, gnomAD rs748617584, REVEL 0.45, ESM-1b 1.00
- M89K (p.Met89Lys), rs772450760, ClinGen CA322220, ClinVar RCV001090985, ExAC rs772450760, REVEL 0.95, ESM-1b 1.00, Uncertain significance, not provided
- M89L (p.Met89Leu), rs2517469704, ClinGen CA410602091, ClinVar RCV002428728, REVEL 0.33, ESM-1b 0.00, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- R91K (p.Arg91Lys), Ensembl rs71322503, REVEL 0.32, ESM-1b 0.00
- K94N (p.Lys94Asn), rs779297627, ClinGen CA410602053, ClinVar RCV002435108, ExAC rs779297627, ESM-1b 0.33, AlphaMissense 0.22, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- I95N (p.Ile95Asn), rs1347662650, ClinGen CA410602048, ClinVar RCV003598641, gnomAD rs1347662650, REVEL 0.95, ESM-1b 1.00, Conflicting interpretations, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED; Classic homocystinuria
- I95T (p.Ile95Thr), rs1347662650, ClinGen CA410602047, ClinVar RCV000557426, ClinVar RCV002232085, REVEL 0.94, ESM-1b 1.00, Conflicting interpretations, Classic homocystinuria; HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
- G96W (p.Gly96Trp), cosmic curated COSV61441, REVEL 0.43, ESM-1b 1.00
- K97N (p.Lys97Asn), TOPMed rs1983106311, ESM-1b 1.00, AlphaMissense 0.25
- K98T (p.Lys98Thr), cosmic curated COSV61444, ESM-1b 0.74, AlphaMissense 0.06
- F99L (p.Phe99Leu), rs749697783, ClinGen CA10583890, ClinVar RCV001854831, ExAC rs749697783, ESM-1b 0.05, AlphaMissense 0.66, Uncertain significance, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
- F99S (p.Phe99Ser), rs112029370, ClinGen CA410602019, ClinVar RCV002048663, ESP rs112029370, REVEL 0.38, ESM-1b 0.00, Uncertain significance, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
- F99Y (p.Phe99Tyr), rs112029370, ClinGen CA16616548, ClinVar RCV000459701, ClinVar RCV000497848, REVEL 0.24, ESM-1b 0.00, Conflicting interpretations, CBS-related disorder; HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED; not specifi
- G100S (p.Gly100Ser), rs1310019343, ClinGen CA410602016, cosmic curated COSV61444, ClinVar RCV002903580, REVEL 0.76, ESM-1b 1.00, Uncertain significance, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
- L101P (p.Leu101Pro), rs786204757, ClinGen CA274473, ClinVar RCV000169617, ClinVar RCV001251397, REVEL 0.97, ESM-1b 1.00, Pathogenic/Likely pathogenic, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED; CBS-related disorder; Homocystinu
- L101V (p.Leu101Val), rs369644531, ClinGen CA10653007, ClinVar RCV000310277, ClinVar RCV002510881, REVEL 0.54, ESM-1b 1.00, Conflicting interpretations, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED; not provided; Classic homocystinu
- K102N (p.Lys102Asn), rs786204609, ClinGen CA274220, ClinVar RCV000169368, ClinVar RCV002444680, ESM-1b 1.00, AlphaMissense 0.33, Uncertain significance, not specified
- K102Q (p.Lys102Gln), rs34040148, ClinGen CA302971, ClinVar RCV000178036, ClinVar RCV000224394, REVEL 0.58, ESM-1b 1.00, Benign/Likely benign, not provided; Connective tissue disorder; not specified
- E104* (p.Glu104Ter), cosmic curated COSV61443
- E104D (p.Glu104Asp), cosmic curated COSV61442, ESM-1b 0.96, AlphaMissense 0.22
- E104K (p.Glu104Lys), cosmic curated COSV61446, ESM-1b 1.00, AlphaMissense 0.34
- L105F (p.Leu105Phe), Ensembl rs1601375543, REVEL 0.78, ESM-1b 1.00, Pathogenic
- L105I (p.Leu105Ile), cosmic curated COSV10065, ESM-1b 1.00, AlphaMissense 0.09
- L105V (p.Leu105Val), rs1601375543, ClinGen CA410601983, ClinVar RCV000794312, ClinVar RCV002233864, REVEL 0.42, ESM-1b 1.00, Uncertain significance, Classic homocystinuria
- L106F (p.Leu106Phe), cosmic curated COSV61441, ESM-1b 1.00, AlphaMissense 0.16
- K108R (p.Lys108Arg), rs2146395442, ClinGen CA410601950, ClinVar RCV002031962, ClinVar RCV003403666, ESM-1b 1.00, AlphaMissense 0.55, Uncertain significance, CBS-related disorder; Classic homocystinuria; HYPERHOMOCYSTEINEMIA, THROMBOTIC
- C109R (p.Cys109Arg), rs778220779, ClinGen CA324303, ClinVar RCV000199752, ClinVar RCV000535881, REVEL 0.98, ESM-1b 1.00, Pathogenic/Likely pathogenic, CBS-related disorder; HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED; Homocystinu
- C109Y (p.Cys109Tyr), rs2517454427, ClinGen CA410601944, ClinVar RCV003599745, REVEL 0.92, ESM-1b 1.00, Likely pathogenic, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
- F111L (p.Phe111Leu), cosmic curated COSV11509, ESM-1b 1.00, AlphaMissense 0.96
- F112L (p.Phe112Leu), gnomAD 21-43055809-A-G, REVEL 0.02, ESM-1b 0.00
- N113K (p.Asn113Lys), gnomAD 21-43055876-A-C, REVEL 0.02, ESM-1b 1.00
- N113S (p.Asn113Ser), rs1330810746, gnomAD 21-43055877-T-C, REVEL 0.02, ESM-1b 0.00
- N113T (p.Asn113Thr), gnomAD 21-43055877-T-G, REVEL 0.03, ESM-1b 1.00
- N113D (p.Asn113Asp), gnomAD 21-43055878-T-C, ESM-1b 1.00, AlphaMissense 0.87
- N113H (p.Asn113His), rs1434749294, gnomAD 21-43055878-T-G, ESM-1b 1.00, AlphaMissense 0.60
- A114E (p.Ala114Glu), cosmic curated COSV10065, ESM-1b 1.00, AlphaMissense 0.92
- A114G (p.Ala114Gly), 1000Genomes rs121964964, ESP rs121964964, ExAC rs121964964, gnomAD rs121964964, ESM-1b 1.00, AlphaMissense 0.31, Pathogenic, in CBSD
- A114S (p.Ala114Ser), rs377708532, ClinGen CA321097892, ClinVar RCV002036189, ExAC rs377708532, REVEL 0.75, ESM-1b 1.00, Likely pathogenic, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
- A114T (p.Ala114Thr), rs377708532, ClinGen CA321097898, cosmic curated COSV10065, ClinVar RCV000493781, REVEL 0.85, ESM-1b 1.00, Conflicting interpretations, CBS-related disorder; Homocystinuria; not provided
- A114V (p.Ala114Val), rs121964964, ClinGen CA113878, cosmic curated COSV61442, ClinVar RCV000000140, REVEL 0.88, ESM-1b 1.00, Pathogenic/Likely pathogenic, CBS-related disorder; Homocystinuria; not provided
- G115D (p.Gly115Asp), rs2517454273, ClinGen CA410601902, ClinVar RCV002740995, ESM-1b 1.00, AlphaMissense 0.98, Uncertain significance, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
- G116R (p.Gly116Arg), rs760214620, ClinGen CA273957, ClinVar RCV000169116, ClinVar RCV001844063, REVEL 0.98, ESM-1b 1.00, Pathogenic, Homocystinuria; Classic homocystinuria; HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RE
- S117C (p.Ser117Cys), rs1982753226, ClinGen CA410601894, ClinVar RCV001138042, ClinVar RCV006465455, ESM-1b 1.00, AlphaMissense 0.75, Uncertain significance, Classic homocystinuria; HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED; Familial
- S117I (p.Ser117Ile), ExAC rs772768738, gnomAD rs772768738, REVEL 0.99, ESM-1b 1.00
- V118A (p.Val118Ala), rs2517454033, ClinGen CA2695201464, ClinVar RCV003460346, ESM-1b 1.00, AlphaMissense 0.50, Likely pathogenic
- V118L (p.Val118Leu), rs763385546, ClinGen CA410601886, ClinVar RCV002459400, REVEL 0.82, ESM-1b 1.00, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- V118M (p.Val118Met), rs763385546, ClinGen CA10644745, NCI-TCGA Cosmic COSV6144, cosmic curated COSV61445, REVEL 0.92, ESM-1b 1.00, Uncertain significance, Classic homocystinuria; HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
- V118F (p.Val118Phe), gnomAD 21-43055869-C-A, REVEL 0.21, ESM-1b 1.00
- V118I (p.Val118Ile), gnomAD 21-43055869-C-T, REVEL 0.17, ESM-1b 0.46
- p.Lys123dup, gnomAD 21-43055890-C-CTT, CADD 3.55
- K119R (p.Lys119Arg), rs750570864, gnomAD 21-43055890-CTT-C, CADD 2.29
- K123del (p.Lys123del), rs750570864, gnomAD 21-43055890-CTTT-, CADD 4.11
- K119K (p.Lys119Lys), rs79861734, gnomAD 21-43055891-T-C, CADD 1.06
- K119N (p.Lys119Asn), gnomAD 21-43055891-T-G, REVEL 0.22, ESM-1b 1.00
- K119T (p.Lys119Thr), rs757998757, gnomAD 21-43055898-T-G, REVEL 0.16, ESM-1b 1.00
- D120G (p.Asp120Gly), rs1982750491, ClinGen CA410601870, cosmic curated COSV61444, ClinVar RCV001344817, ESM-1b 1.00, AlphaMissense 0.97, Likely pathogenic, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED; not provided
- D120N (p.Asp120Asn), gnomAD rs1251292223, REVEL 0.92, ESM-1b 1.00, Conflicting interpretations, HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED; not provided
- D120E (p.Asp120Glu), gnomAD 21-43055888-A-C, REVEL 0.04, ESM-1b 1.00
- D120D (p.Asp120Asp), rs1601326852, gnomAD 21-43055888-A-G, CADD 2.26
- D120V (p.Asp120Val), rs767504311, gnomAD 21-43055888-AT-A, CADD 0.23
- D120A (p.Asp120Ala), gnomAD 21-43055889-T-G, REVEL 0.01, ESM-1b 1.00
- D120M (p.Asp120Met), rs1218599058, gnomAD 21-43055889-TC-T, CADD 1.37
- D120R (p.Asp120Arg), rs750570864, gnomAD 21-43055890-C-CT, CADD 4.03
Public CBS analysis runs
- CBS analysis run — CBS (1,002 variants) — completed 2026-10-09