SOX9 p.Ala331=
c.993G>A · rs761105285 · VCV324917
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.121%, nfe)
Conditions
1
campomelic dysplasia
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 -1.8 | GERP -3.3 |
| Overall | ||
| CADD | 6.48 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.121%
European (non-Finnish) · 1,420/1,170,226 alleles
Filtering AF
0.116%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.114%
Overall
0.0928%
1,476/1,591,168 alleles · rare
exomes 1,412/1,439,374 · genomes 64/151,794 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.121% | 824 |
| Remaining individualsnot grpmax-eligible | 0.0682% | 1,467 |
| African / African-American | 0.0121% | 8,261 |
| Admixed American | 0.00692% | 14,454 |
| Finnishnot grpmax-eligible | 0.00174% | 57,458 |
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
- SOX9
- Protein
- p.Ala331=
- Coding
- c.993G>A
- MANE Select
- NM_000346
- dbSNP
- rs761105285
- Type
- single nucleotide variant
- Location
- chr17:72123850 (GRCh38)
- Gene constraint
- LOEUF 0.154 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 56.69 · 1 PDB
- Residue 331
- a UniProt-annotated variant site (in cmd1); the 'disordered' region
Similar variants
- SOX9 p.Ala331Thr Likely benign ★ same residue
- SOX9 p.Ala331Val Likely benign ★ same residue
- SOX9 c.432-2A>T Pathogenic ★★ same condition
- SOX9 p.Ala158Val Pathogenic/Likely pathogenic ★★ same condition
- SOX9 p.Arg152Pro Pathogenic/Likely pathogenic ★★ same condition
- SOX9 p.Arg394Ter Pathogenic ★★ same condition
- SOX9 p.Gln340Ter Pathogenic/Likely pathogenic ★★ same condition
- SOX9 p.Gln357Ter 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/sox9-p-ala331 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown