Is SOX2 p.Phe48Val (c.142T>G) pathogenic?

SOX2 p.Phe48Val (c.142T>G) is classified Likely pathogenic in SOX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-10-02). AlphaMissense: likely pathogenic (1); Absent from gnomAD v4.1; Associated with anophthalmia/microphthalmia-esophageal atresia syndrome.

What condition is associated with SOX2 p.Phe48Val (c.142T>G)?

SOX2 p.Phe48Val (c.142T>G) is associated with anophthalmia/microphthalmia-esophageal atresia syndrome (ClinVar).

How common is SOX2 p.Phe48Val (c.142T>G) in the general population?

SOX2 p.Phe48Val (c.142T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SOX2 p.Phe48Val (c.142T>G)?

AlphaMissense predicts likely pathogenic (score 1) — an in-silico prediction, not a clinical call.

SOX2 p.Phe48Val

c.142T>G · rs2473717249 · VCV3062095

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

1 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

anophthalmia/microphthalmia-esophageal atresia syndrome

Computational evidence

Protein change
AlphaMissense	1	likely pathogenic ✓ concordant with ClinVar
REVEL	0.985	strongly pathogenic-leaning
SaProt	LLR -15.33	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.5, phastCons 1
Regional constraint	o/e 0.18	constrained · MANE · 232 bp · p 3.1e-18 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SOX2
Protein: p.Phe48Val
Coding: c.142T>G
MANE Select: NM_003106
dbSNP: rs2473717249
Type: single nucleotide variant
Location: chr3:181712502 (GRCh38)
Gene constraint: LOEUF 0.302 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.91 · 13 PDB
Residue 48: a DNA-binding region; an α-helix

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.Phe48del Pathogenic ★ same residue
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.Ala281= Likely benign ★★ same condition
SOX2 p.Ala287= Benign/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-phe48val (accessed [today's date]).

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