Is SOX9 p.Pro370= (c.1110G>A) pathogenic?

SOX9 p.Pro370= (c.1110G>A) is classified Likely benign in SOX9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-25). Very rare (popmax 9e-05%, nfe); Associated with campomelic dysplasia.

What condition is associated with SOX9 p.Pro370= (c.1110G>A)?

SOX9 p.Pro370= (c.1110G>A) is associated with campomelic dysplasia (ClinVar).

How common is SOX9 p.Pro370= (c.1110G>A) in the general population?

SOX9 p.Pro370= (c.1110G>A) is very rare (popmax 9e-05%, nfe) (gnomAD).

SOX9 p.Pro370=

c.1110G>A · VCV3705391

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 9e-05%, nfe)

Conditions

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 -1.5	GERP -2.8, phastCons 0.002
Overall
CADD	3.831	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9e-05% European (non-Finnish) · 1/1,111,466 alleles

Overall 0.000136% 2/1,467,794 alleles · very rare exomes 2/1,316,504 · genomes 0/151,290 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00179%	55,744
European (non-Finnish)grpmax	9e-05%	1,111,466

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro370=
Coding: c.1110G>A
MANE Select: NM_000346
Type: single nucleotide variant
Location: chr17:72123967 (GRCh38)
Gene constraint: LOEUF 0.154 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 56.69 · 1 PDB
Residue 370: a UniProt-annotated variant site (in cmd1); the 'disordered' region

Full SOX9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

campomelic dysplasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SOX9 p.Pro370Leu 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
SOX9 p.Glu148Ter 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-pro370 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown