SMC3 p.Ala293=
c.879T>C · VCV4809359
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Conditions
1
Cornelia de Lange syndrome 3
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.17 | GERP -2.6, phastCons 0.73 |
| Overall | ||
| CADD | 7.908 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,034 alleles
Overall
0.000186%
3/1,614,036 alleles · very rare
exomes 3/1,461,738 · genomes 0/152,298 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 60,034 |
| South Asian | 0.0011% | 91,080 |
| European (non-Finnish) | 8.48e-05% | 1,179,924 |
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
- SMC3
- Protein
- p.Ala293=
- Coding
- c.879T>C
- MANE Select
- NM_005445
- Type
- single nucleotide variant
- Location
- chr10:110583458 (GRCh38)
- Gene constraint
- LOEUF 0.132 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 82.37 · 12 PDB
Similar variants
- SMC3 p.Ala293Thr Uncertain significance ★ ⚠ same residue
- SMC3 p.Gln1147Glu Pathogenic ★★ same condition
- SMC3 p.Glu95Lys Likely pathogenic ★★ same condition
- SMC3 p.Ile196Thr Pathogenic/Likely pathogenic ★★ same condition
- SMC3 p.Met648Val Pathogenic/Likely pathogenic ★★ same condition
- SMC3 p.Trp473Gly Likely pathogenic ★★ same condition
- SMC3 c.430-3T>C Uncertain significance ★★ same condition
- SMC3 p.Ala484Gly Uncertain significance ★★ ⚠ 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/smc3-p-ala293 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown