Is SOX10 p.Pro175Ser (c.523C>T) pathogenic?

SOX10 p.Pro175Ser (c.523C>T) is classified Pathogenic/Likely pathogenic in SOX10 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-18). AlphaMissense: likely pathogenic (0.9997); Absent from gnomAD v4.1; Associated with Waardenburg syndrome type 2E.

What condition is associated with SOX10 p.Pro175Ser (c.523C>T)?

SOX10 p.Pro175Ser (c.523C>T) is associated with Waardenburg syndrome type 2E (ClinVar).

How common is SOX10 p.Pro175Ser (c.523C>T) in the general population?

SOX10 p.Pro175Ser (c.523C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SOX10 p.Pro175Ser (c.523C>T)?

AlphaMissense predicts likely pathogenic (score 0.9997) — an in-silico prediction, not a clinical call.

SOX10 p.Pro175Ser

c.523C>T · rs1555938395 · VCV521356

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9997 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Waardenburg syndrome type 2E

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.9997	likely pathogenic ✓ concordant with ClinVar
REVEL	0.825	moderately pathogenic-leaning
SaProt	LLR -15.70	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.34	constrained · MANE · 5,544 bp · p 2.3e-16 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SOX10
Protein: p.Pro175Ser
Coding: c.523C>T
MANE Select: NM_006941
dbSNP: rs1555938395
Type: single nucleotide variant
Location: chr22:37978041 (GRCh38)

Full SOX10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Waardenburg syndrome type 2E — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/sox10-p-pro175ser (accessed [today's date]).

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