Is SOX4 p.Arg110= (c.330A>G) pathogenic?

SOX4 p.Arg110= (c.330A>G) is classified Likely benign in SOX4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-09). Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SOX4 p.Arg110= (c.330A>G)?

SOX4 p.Arg110= (c.330A>G) is associated with Inborn genetic diseases (ClinVar).

How common is SOX4 p.Arg110= (c.330A>G) in the general population?

SOX4 p.Arg110= (c.330A>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

SOX4 p.Arg110=

c.330A>G · VCV3447508

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP -4.2, phastCons 1
Overall
CADD	12.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,518 alleles

Overall 6.2e-05% 1/1,612,648 alleles · very rare exomes 0/1,460,312 · genomes 1/152,336 · joint denominator

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.Arg110=
Coding: c.330A>G
MANE Select: NM_003107
Type: single nucleotide variant
Location: chr6:21594864 (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.Arg110Pro Uncertain significance ★★ ⚠ 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-arg110 (accessed [today's date]).

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