Is SOX10 p.Leu129Pro (c.386T>C) pathogenic?

SOX10 p.Leu129Pro (c.386T>C) is classified Likely pathogenic in SOX10 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-01). AlphaMissense: likely pathogenic (1); No allele count reported in gnomAD v4.1 (AN 1,610,322); Associated with Waardenburg syndrome type 2E.

What condition is associated with SOX10 p.Leu129Pro (c.386T>C)?

SOX10 p.Leu129Pro (c.386T>C) is associated with Waardenburg syndrome type 2E (ClinVar).

How common is SOX10 p.Leu129Pro (c.386T>C) in the general population?

SOX10 p.Leu129Pro (c.386T>C) is no allele count reported in gnomAD v4.1 (AN 1,610,322) (gnomAD).

What do computational predictors say about SOX10 p.Leu129Pro (c.386T>C)?

AlphaMissense predicts likely pathogenic (score 1) — an in-silico prediction, not a clinical call.

SOX10 p.Leu129Pro

c.386T>C · rs1932462410 · VCV995933

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

1 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,610,322)

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	1	likely pathogenic ✓ concordant with ClinVar
REVEL	0.953	strongly pathogenic-leaning
SaProt	LLR -16.21	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	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	34.0	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

No allele count reported in gnomAD v4.1 (AN 1,610,322). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SOX10
Protein: p.Leu129Pro
Coding: c.386T>C
MANE Select: NM_006941
dbSNP: rs1932462410
Type: single nucleotide variant
Location: chr22:37983399 (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-leu129pro (accessed [today's date]).

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