Congenital muscular hypertrophy-cerebral syndrome: genes and variants
Explore variant evidence for Congenital muscular hypertrophy-cerebral syndrome across 1 analyzed protein (SMC1A). Linked ClinVar records include 39 pathogenic or likely pathogenic variants, 139 variants of uncertain significance and 26 with conflicting classifications.
Coverage includes proteins already analyzed in CATVariant, not every gene involved in this condition. Database links are associations, not an assessment of clinical gene–disease validity. Computable evidence prioritizes variants for expert review and does not reclassify them. Counts refer to the selected disease label.
Data updated 2026-10-11. Automated aggregation, not a clinical review date.
Download variant evidence (CSV)
Genes linked to Congenital muscular hypertrophy-cerebral syndrome
SMC1A: Structural maintenance of chromosomes protein 1A
A core cohesin protein that helps hold sister chromatids together and organize DNA. Variants can cause Cornelia de Lange syndrome or developmental epilepsy.
39 ClinVar pathogenic / likely pathogenic and 165 uncertain variants in SMC1A have source records linked to Congenital muscular hypertrophy-cerebral syndrome. Association strength is not clinical gene validity.
ClinVar pathogenic and likely pathogenic variants linked to Congenital muscular hypertrophy-cerebral syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| SMC1A R496C | 496 | Coiled coil | Pathogenic / likely pathogenic (★★) |
| SMC1A R496H | 496 | Coiled coil | Pathogenic / likely pathogenic (★★) |
| SMC1A R196H | 196 | Coiled coil | Pathogenic / likely pathogenic (★★) |
| SMC1A R1066H | 1066 | Coiled coil | Pathogenic / likely pathogenic (★★) |
| SMC1A R586W | 586 | SMC hinge | Pathogenic / likely pathogenic (★★) |
| SMC1A R711Q | 711 | Coiled coil | Pathogenic / likely pathogenic (★★) |
| SMC1A F777L | 777 | Coiled coil | Pathogenic / likely pathogenic (★★) |
| SMC1A I784T | 784 | Coiled coil | Pathogenic / likely pathogenic (★★) |
| SMC1A Y983C | 983 | Pathogenic / likely pathogenic (★★) | |
| SMC1A C1115F | 1115 | Pathogenic / likely pathogenic (★) | |
| SMC1A C1115Y | 1115 | Pathogenic / likely pathogenic (★) | |
| SMC1A G32E | 32 | Pathogenic / likely pathogenic (★) | |
| SMC1A D43N | 43 | Pathogenic / likely pathogenic (★) | |
| SMC1A D43V | 43 | Pathogenic / likely pathogenic (★) | |
| SMC1A F133V | 133 | Pathogenic / likely pathogenic (★) | |
| SMC1A R196G | 196 | Coiled coil | Pathogenic / likely pathogenic (★) |
| SMC1A P572S | 572 | SMC hinge | Pathogenic / likely pathogenic (★) |
| SMC1A P572L | 572 | SMC hinge | Pathogenic / likely pathogenic (★) |
| SMC1A S653F | 653 | Pathogenic / likely pathogenic (★) | |
| SMC1A G654V | 654 | Pathogenic / likely pathogenic (★) | |
| SMC1A G655E | 655 | Pathogenic / likely pathogenic (★) | |
| SMC1A R1066S | 1066 | Coiled coil | Pathogenic / likely pathogenic (★) |
| SMC1A R1123W | 1123 | Pathogenic / likely pathogenic (★) | |
| SMC1A M1125V | 1125 | Pathogenic / likely pathogenic (★) | |
| SMC1A V1154D | 1154 | Pathogenic / likely pathogenic (★) | |
| SMC1A N1166T | 1166 | Pathogenic / likely pathogenic (★) | |
| SMC1A K1190Q | 1190 | Pathogenic / likely pathogenic (★) | |
| SMC1A G37V | 37 | Pathogenic / likely pathogenic (★) | |
| SMC1A R96C | 96 | Pathogenic / likely pathogenic (★) | |
| SMC1A E303D | 303 | Coiled coil | Pathogenic / likely pathogenic (★) |
| SMC1A E368K | 368 | Coiled coil | Pathogenic / likely pathogenic (★) |
| SMC1A K536R | 536 | SMC hinge | Pathogenic / likely pathogenic (★) |
| SMC1A R693G | 693 | Coiled coil | Pathogenic / likely pathogenic (★) |
| SMC1A D774Y | 774 | Coiled coil | Pathogenic / likely pathogenic (★) |
| SMC1A E1040K | 1040 | Coiled coil | Pathogenic / likely pathogenic (★) |
| SMC1A L1141P | 1141 | Pathogenic / likely pathogenic (★) | |
| SMC1A E493A | 493 | Coiled coil | Pathogenic / likely pathogenic |
| SMC1A C781R | 781 | Coiled coil | Pathogenic / likely pathogenic |
| SMC1A R807H | 807 | Coiled coil | Pathogenic / likely pathogenic |
Uncertain variants prioritized for review in Congenital muscular hypertrophy-cerebral syndrome
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| SMC1A N1166S | 1166 | Conflicting reports (★) | +6: in a 3D region that tolerates change poorly (1A); N1166T at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 0.99 | |
| SMC1A D774N | 774 | Coiled coil | Uncertain (★) | +6: 2 other pathogenic changes within 3 positions; D774Y at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 0.99 |
Which prediction tools work for Congenital muscular hypertrophy-cerebral syndrome
Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.
- PolyPhen-2: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 97 out of 100
- ESM1b (LLR): 96 out of 100
- CATVariant: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- AlphaMissense: 93 out of 100
- MetaLR: 92 out of 100 (learned from overlapping clinical labels, so this is optimistic)
Diseases related to Congenital muscular hypertrophy-cerebral syndrome
- Cornelia de Lange syndrome, also linked to SMC1A
- Developmental and epileptic encephalopathy, 85, with or without midline brain defects, also linked to SMC1A
- Genetic developmental and epileptic encephalopathy, also linked to SMC1A
Frequently asked questions
Which genes have records linked to Congenital muscular hypertrophy-cerebral syndrome?
This view contains 1 analyzed proteins: SMC1A. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.
What do the clinical classifications mean?
Linked records include 39 pathogenic or likely pathogenic variants, 139 variants of uncertain significance and 26 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.
Does the evidence score change a VUS classification?
No. 2 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.
Can I download the variant evidence?
Download the CSV for all 216 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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