SOX9 p.Pro354=
c.1062G>C · rs868845946 · VCV2063208
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0275%, mid)
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 -0.21 | GERP -2.6 |
| Overall | ||
| CADD | 9.145 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0275%
Middle Eastern · 1/3,636 alleles
Filtering AF
0.00334%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00182%
Overall
0.00062%
8/1,289,864 alleles · ultra-rare
exomes 7/1,139,002 · genomes 1/150,862 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0275% | 3,636 |
| Admixed American | 0.0126% | 7,928 |
| European (non-Finnish) | 0.000389% | 256,765 |
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.Pro354=
- Coding
- c.1062G>C
- MANE Select
- NM_000346
- dbSNP
- rs868845946
- Type
- single nucleotide variant
- Location
- chr17:72123919 (GRCh38)
- Gene constraint
- LOEUF 0.154 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 56.69 · 1 PDB
- Residue 354
- a UniProt-annotated variant site (in cmd1); the 'disordered' region
Similar variants
- SOX9 p.Pro354Leu Uncertain significance ★ ⚠ same residue
- SOX9 p.Pro354Ser Benign ★ same residue
- SOX9 p.Pro354_Pro356del Benign/Likely benign ★★ same residue
- SOX9 p.Pro354Thr 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
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-pro354 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown