Is SOX4 p.Ser32Ala (c.94T>G) pathogenic?

SOX4 p.Ser32Ala (c.94T>G) is classified Uncertain significance in SOX4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-01). AlphaMissense: likely benign (0.1846); Very rare (popmax 0.00926%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SOX4 p.Ser32Ala (c.94T>G)?

SOX4 p.Ser32Ala (c.94T>G) is associated with Inborn genetic diseases (ClinVar).

How common is SOX4 p.Ser32Ala (c.94T>G) in the general population?

SOX4 p.Ser32Ala (c.94T>G) is very rare (popmax 0.00926%, nfe) (gnomAD).

What do computational predictors say about SOX4 p.Ser32Ala (c.94T>G)?

AlphaMissense predicts likely benign (score 0.1846) — an in-silico prediction, not a clinical call.

SOX4 p.Ser32Ala

c.94T>G · VCV4631868

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1846 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00926%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1846	likely benign
REVEL	0.277	benign-leaning
SaProt	LLR -6.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 0.98, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 165 bp · p 0.38 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00926% European (non-Finnish) · 109/1,177,444 alleles

Filtering AF 0.00784% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00729%

Overall 0.00691% 111/1,606,292 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00926%	10,802
African / African-American	0.00268%	37,343

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: SOX4
Protein: p.Ser32Ala
Coding: c.94T>G
MANE Select: NM_003107
Type: single nucleotide variant
Location: chr6:21594628 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI 0.79 (gnomAD)
Structure: AlphaFold pLDDT 55.71
Residue 32: the 'disordered' region

Full SOX4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SOX4 p.Ala145Thr Uncertain significance ★★ ⚠ same condition
SOX4 p.Ala253Val Uncertain significance ★★ ⚠ same condition
SOX4 p.Arg110Pro Uncertain significance ★★ ⚠ same condition
SOX4 p.Gly226Ser Uncertain significance ★★ ⚠ same condition
SOX4 p.Leu100Phe Uncertain significance ★★ ⚠ same condition
SOX4 p.Pro214Ser Uncertain significance ★★ ⚠ same condition
SOX4 p.Arg110= Likely benign ★★ same condition
SOX4 p.Ala112Val Conflicting classifications of pathogenicity ★ ⚠ 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/sox4-p-ser32ala (accessed [today's date]).

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