Is SOX10 p.Phe153Ile (c.457T>A) pathogenic?

SOX10 p.Phe153Ile (c.457T>A) is classified Uncertain significance in SOX10 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-07-29). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1.

How common is SOX10 p.Phe153Ile (c.457T>A) in the general population?

SOX10 p.Phe153Ile (c.457T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SOX10 p.Phe153Ile (c.457T>A)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

SOX10 p.Phe153Ile

c.457T>A · rs2145768609 · VCV1304154

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

⚠ 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	0.9999	likely pathogenic
REVEL	0.963	strongly pathogenic-leaning
SaProt	LLR -13.79	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.4	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	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Phe153Ile
Coding: c.457T>A
MANE Select: NM_006941
dbSNP: rs2145768609
Type: single nucleotide variant
Location: chr22:37978107 (GRCh38)

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

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-phe153ile (accessed [today's date]).

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