SOX9 p.Pro356=
c.1068G>A · rs1319508171 · VCV2781525
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00624%, eas)
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 -0.41 | GERP -3.3 |
| Overall | ||
| CADD | 7.228 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00624%
East Asian · 2/32,034 alleles
Filtering AF
0.00103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000387%
Overall
0.000775%
10/1,289,840 alleles · very rare
exomes 9/1,138,916 · genomes 1/150,924 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00624% | 16,017 |
| European (non-Finnish) | 0.000779% | 128,370 |
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.Pro356=
- Coding
- c.1068G>A
- MANE Select
- NM_000346
- dbSNP
- rs1319508171
- Type
- single nucleotide variant
- Location
- chr17:72123925 (GRCh38)
- Gene constraint
- LOEUF 0.154 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 56.69 · 1 PDB
- Residue 356
- a UniProt-annotated variant site (in cmd1); the 'disordered' region
Similar variants
- SOX9 p.Pro356Leu Uncertain significance ★ ⚠ same residue
- SOX9 p.Pro356_Gln357insProAlaPro Uncertain significance ★★ 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-pro356 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown