SOX2 p.Ala281=
c.843C>T · rs1453651086 · VCV2189126
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Conditions
1
anophthalmia/microphthalmia-esophageal atresia syndrome
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 1.1 | GERP -0.5, phastCons 1 |
| Overall | ||
| CADD | 12.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,012 alleles
Overall
6.85e-05%
1/1,460,638 alleles · very rare
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
- SOX2
- Protein
- p.Ala281=
- Coding
- c.843C>T
- MANE Select
- NM_003106
- dbSNP
- rs1453651086
- Type
- single nucleotide variant
- Location
- chr3:181713203 (GRCh38)
- Gene constraint
- LOEUF 0.302 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 61.91 · 13 PDB
Similar variants
- SOX2 p.Glu8Ter Pathogenic/Likely pathogenic ★★ same condition
- SOX2 p.Tyr207Ter Pathogenic/Likely pathogenic ★★ same condition
- SOX2 p.Gly142Arg Uncertain significance ★★ ⚠ same condition
- SOX2 p.Pro264Thr Uncertain significance ★★ ⚠ same condition
- SOX2 p.Thr26Ala Uncertain significance ★★ ⚠ same condition
- SOX2 p.Ala287= Benign/Likely benign ★★ same condition
- SOX2 p.Asn164= Likely benign ★★ same condition
- SOX2 p.Asn187= Likely benign ★★ 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/sox2-p-ala281 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown