Is SOX4 p.Pro62Arg (c.185C>G) pathogenic?

SOX4 p.Pro62Arg (c.185C>G) is classified Likely pathogenic in SOX4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-10). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1; Associated with Coffin-Siris syndrome 10.

What condition is associated with SOX4 p.Pro62Arg (c.185C>G)?

SOX4 p.Pro62Arg (c.185C>G) is associated with Coffin-Siris syndrome 10 (ClinVar).

How common is SOX4 p.Pro62Arg (c.185C>G) in the general population?

SOX4 p.Pro62Arg (c.185C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SOX4 p.Pro62Arg (c.185C>G)?

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

SOX4 p.Pro62Arg

c.185C>G · VCV3774374

Likely pathogenic Single submitter

Classification

Likely pathogenic

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

Conditions

Coffin-Siris syndrome 10

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic ✓ concordant with ClinVar · top 7% in SOX4
REVEL	0.983	strongly pathogenic-leaning
SaProt	LLR -15.89	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	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

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.Pro62Arg
Coding: c.185C>G
MANE Select: NM_003107
Type: single nucleotide variant
Location: chr6:21594719 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI 0.79 (gnomAD)
Structure: AlphaFold pLDDT 55.71
Residue 62: a DNA-binding region

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

Disease context

Coffin-Siris syndrome 10 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SOX4 p.Pro62Leu Likely pathogenic ★ same residue
SOX4 p.Gln241Ter Likely pathogenic ★★ same condition
SOX4 p.Ser347Ter Pathogenic/Likely pathogenic ★★ same condition
SOX4 p.Ala231Thr Uncertain significance ★★ ⚠ same condition
SOX4 p.Ser338Gly Likely benign ★★ same condition
SOX4 p.Ala112Glu Likely pathogenic ★ same condition
SOX4 p.Glu445Ter Pathogenic ★ same condition
SOX4 p.Gly94Asp Likely pathogenic ★ 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-pro62arg (accessed [today's date]).

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