SMC1A p.Lys897=
c.2691A>G · rs782574044 · VCV759135
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0109%, nfe)
Conditions
1
Cornelia de Lange syndrome 2
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.21 | donor loss · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.8 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 8.316 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0109%
European (non-Finnish) · 98/895,023 alleles
Filtering AF
0.00919%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00844%
Overall
0.00835%
101/1,208,972 alleles · ultra-rare
exomes 94/1,098,000 · genomes 7/110,972 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0109% | 9,133 |
| Admixed American | 0.00439% | 22,773 |
| Remaining individualsnot grpmax-eligible | 0.0021% | 47,572 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- SMC1A
- Protein
- p.Lys897=
- Coding
- c.2691A>G
- MANE Select
- NM_006306
- dbSNP
- rs782574044
- Type
- single nucleotide variant
- Location
- chrX:53396489 (GRCh38)
- Structure
- AlphaFold pLDDT 83.02 · 18 PDB
- Residue 897
- an α-helix; a UniProt-annotated variant site (in dee85)
Similar variants
- SMC1A c.1114-2A>G Pathogenic ★★ same condition
- SMC1A c.1546-2A>C Likely pathogenic ★★ same condition
- SMC1A p.Arg1035Ter Pathogenic/Likely pathogenic ★★ same condition
- SMC1A p.Arg1049Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
- SMC1A p.Arg1049Ter Pathogenic ★★ same condition
- SMC1A p.Arg1066Cys Pathogenic/Likely pathogenic ★★ same condition
- SMC1A p.Arg1066His Pathogenic/Likely pathogenic ★★ same condition
- SMC1A p.Arg171Ter Pathogenic ★★ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/smc1a-p-lys897 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown