Is SOX2 p.Pro253fs (c.758del) pathogenic?

SOX2 p.Pro253fs (c.758del) is classified Likely pathogenic in SOX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-13). Associated with anophthalmia/microphthalmia-esophageal atresia syndrome.

What condition is associated with SOX2 p.Pro253fs (c.758del)?

SOX2 p.Pro253fs (c.758del) is associated with anophthalmia/microphthalmia-esophageal atresia syndrome (ClinVar).

SOX2 p.Pro253fs

c.758del · VCV3338557

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

anophthalmia/microphthalmia-esophageal atresia syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon in the last exon (1 of 1) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.9	GERP 2.3, phastCons 1
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: SOX2
Protein: p.Pro253fs
Coding: c.758del
MANE Select: NM_003106
Type: Deletion
Location: chr3:181713113 (GRCh38)
Gene constraint: LOEUF 0.302 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.91 · 13 PDB
Residue 253: the 'disordered' region

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

Similar variants

SOX2 p.Glu8_Leu9insTer Pathogenic ★ same condition
SOX2 p.Phe48del Pathogenic ★ same condition
SOX2 p.Pro181fs Pathogenic ★ same condition
SOX2 p.Ser259fs Likely pathogenic ★ same condition
SOX2 p.Pro253Ala Uncertain significance ★ ⚠ same residue
SOX2 p.Gly20fs Pathogenic same condition
SOX2 p.Gly280fs Pathogenic same condition
SOX2 p.Met1fs 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/sox2-p-pro253fs (accessed [today's date]).

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