Is SOX2 p.Pro12= (c.36G>C) pathogenic?

SOX2 p.Pro12= (c.36G>C) is classified Uncertain significance in SOX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-09). Very rare (popmax 0.00817%, afr); Associated with anophthalmia/microphthalmia-esophageal atresia syndrome.

What condition is associated with SOX2 p.Pro12= (c.36G>C)?

SOX2 p.Pro12= (c.36G>C) is associated with anophthalmia/microphthalmia-esophageal atresia syndrome (ClinVar).

How common is SOX2 p.Pro12= (c.36G>C) in the general population?

SOX2 p.Pro12= (c.36G>C) is very rare (popmax 0.00817%, afr) (gnomAD).

SOX2 p.Pro12=

c.36G>C · VCV3705509

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00817%, afr)

Conditions

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 looked up on this page · why
Constraint at this position
Conservation	phyloP 1.9	GERP -3, phastCons 1
Overall
CADD	12.68	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00817% African / African-American · 6/73,418 alleles

Filtering AF 0.00353% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.000761% 12/1,577,012 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00817%	12,236
East Asian	0.00704%	14,200
Remaining individualsnot grpmax-eligible	0.00164%	60,960
South Asian	0.00114%	88,062
European (non-Finnish)	8.6e-05%	1,162,156

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.Pro12=
Coding: c.36G>C
Type: single nucleotide variant
Location: chr3:181712396 (GRCh38)

Full SOX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

anophthalmia/microphthalmia-esophageal atresia syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-pro12 (accessed [today's date]).

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