Is SOX4 p.Arg110Pro (c.329G>C) pathogenic?

SOX4 p.Arg110Pro (c.329G>C) is classified Uncertain significance in SOX4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-28). AlphaMissense: likely pathogenic (0.9996); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SOX4 p.Arg110Pro (c.329G>C)?

SOX4 p.Arg110Pro (c.329G>C) is associated with Inborn genetic diseases (ClinVar).

How common is SOX4 p.Arg110Pro (c.329G>C) in the general population?

SOX4 p.Arg110Pro (c.329G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SOX4 p.Arg110Pro (c.329G>C)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

SOX4 p.Arg110Pro

c.329G>C · VCV3321646

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic · top 7% in SOX4
REVEL	0.679	pathogenic-leaning
SaProt	LLR -17.70	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 8.1	GERP 2.4, phastCons 1
Regional constraint	o/e 0.38	unconstrained · MANE · 232 bp · p 7.6e-11 · regional, not allelic
Overall
CADD	34.0	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.Arg110Pro
Coding: c.329G>C
MANE Select: NM_003107
Type: single nucleotide variant
Location: chr6:21594863 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI 0.79 (gnomAD)
Structure: AlphaFold pLDDT 55.71
Residue 110: a DNA-binding 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.Arg110= Likely benign ★★ same residue
SOX4 p.Ala145Thr Uncertain significance ★★ ⚠ same condition
SOX4 p.Ala253Val 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.Ser32Ala Uncertain significance ★★ ⚠ 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-arg110pro (accessed [today's date]).

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