Is SOX4 p.Pro82Ser (c.244C>T) pathogenic?

SOX4 p.Pro82Ser (c.244C>T) is classified Uncertain significance in SOX4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-12). AlphaMissense: likely pathogenic (0.9985); Absent from gnomAD v4.1.

How common is SOX4 p.Pro82Ser (c.244C>T) in the general population?

SOX4 p.Pro82Ser (c.244C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SOX4 p.Pro82Ser (c.244C>T)?

AlphaMissense predicts likely pathogenic (score 0.9985) — an in-silico prediction, not a clinical call.

SOX4 p.Pro82Ser

c.244C>T · rs868783682 · VCV2662322

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9985 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9985	likely pathogenic · top 10% in SOX4
REVEL	0.864	moderately pathogenic-leaning
SaProt	LLR -14.27	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 2.4, phastCons 1
Regional constraint	o/e 0.38	unconstrained · MANE · 232 bp · p 7.6e-11 · regional, not allelic
Overall
CADD	33.0	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: SOX4
Protein: p.Pro82Ser
Coding: c.244C>T
MANE Select: NM_003107
dbSNP: rs868783682
Type: single nucleotide variant
Location: chr6:21594778 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI 0.79 (gnomAD)
Structure: AlphaFold pLDDT 55.71
Residue 82: a DNA-binding region

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

Similar variants

SOX4 p.Gln241Ter Likely pathogenic ★★ same type
SOX4 p.Ser347Ter Pathogenic/Likely pathogenic ★★ same type
SOX4 p.Ala145Thr Uncertain significance ★★ ⚠ same type
SOX4 p.Ala231Thr Uncertain significance ★★ ⚠ same type
SOX4 p.Ala234Pro Uncertain significance ★★ ⚠ same type
SOX4 p.Ala253Val Uncertain significance ★★ ⚠ same type
SOX4 p.Arg110Pro Uncertain significance ★★ ⚠ same type
SOX4 p.Gly226Ser Uncertain significance ★★ ⚠ same type

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-pro82ser (accessed [today's date]).

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