SOX4 p.Arg75=
c.225C>A · VCV4973876
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00352%, amr)
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 0.46 | GERP -3.3, phastCons 1 |
| Overall | ||
| CADD | 14.1 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00352%
Admixed American · 2/56,896 alleles
Filtering AF
0.000583%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000218%
Overall
0.000188%
3/1,599,692 alleles · very rare
exomes 0/1,447,452 · genomes 3/152,240 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00352% | 28,448 |
| European (non-Finnish) | 8.52e-05% | 1,173,387 |
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.Arg75=
- Coding
- c.225C>A
- MANE Select
- NM_003107
- Type
- single nucleotide variant
- Location
- chr6:21594759 (GRCh38)
- Gene constraint
- LOEUF 0.72 · pLI 0.79 (gnomAD)
- Structure
- AlphaFold pLDDT 55.71
- Residue 75
- a DNA-binding region
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-arg75 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown