SOX9 p.Pro374=
c.1122G>T · VCV4936823
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00974%, amr)
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 0.028 | GERP -1.7, phastCons 0.006 |
| Overall | ||
| CADD | 8.805 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00974%
Admixed American · 5/51,330 alleles
Filtering AF
0.0038%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00246%
Overall
0.000397%
6/1,512,418 alleles · very rare
exomes 6/1,360,912 · genomes 0/151,506 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00974% | 10,266 |
| European (non-Finnish) | 8.83e-05% | 1,133,037 |
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.Pro374=
- Coding
- c.1122G>T
- MANE Select
- NM_000346
- Type
- single nucleotide variant
- Location
- chr17:72123979 (GRCh38)
- Gene constraint
- LOEUF 0.154 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 56.69 · 1 PDB
- Residue 374
- a UniProt-annotated variant site (in cmd1); the 'disordered' region
Similar variants
- SOX9 p.Pro374fs Pathogenic ★ same residue
- SOX9 c.432-2A>T Pathogenic ★★ same type
- SOX9 p.Ala158Val Pathogenic/Likely pathogenic ★★ same type
- SOX9 p.Arg152Pro Pathogenic/Likely pathogenic ★★ same type
- SOX9 p.Arg394Ter Pathogenic ★★ same type
- SOX9 p.Gln340Ter Pathogenic/Likely pathogenic ★★ same type
- SOX9 p.Gln357Ter Pathogenic ★★ same type
- SOX9 p.Glu148Ter Pathogenic ★★ same type
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-pro374 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown