Is FOXE3 p.Val130Phe (c.388G>T) pathogenic?

FOXE3 p.Val130Phe (c.388G>T) is classified Likely pathogenic in FOXE3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-05-02). AlphaMissense: likely pathogenic (0.9393); Absent from gnomAD v4.1; Associated with congenital primary aphakia.

What condition is associated with FOXE3 p.Val130Phe (c.388G>T)?

FOXE3 p.Val130Phe (c.388G>T) is associated with congenital primary aphakia (ClinVar).

How common is FOXE3 p.Val130Phe (c.388G>T) in the general population?

FOXE3 p.Val130Phe (c.388G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FOXE3 p.Val130Phe (c.388G>T)?

AlphaMissense predicts likely pathogenic (score 0.9393) — an in-silico prediction, not a clinical call.

FOXE3 p.Val130Phe

c.388G>T · rs1646884931 · VCV1710250

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9393 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital primary aphakia

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.9393	likely pathogenic ✓ concordant with ClinVar
REVEL	0.743	pathogenic-leaning
SaProt	LLR -12.92	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.2	GERP -3.6, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 956 bp · p 0.59 · regional, not allelic
Overall
CADD	34.0	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: FOXE3
Protein: p.Val130Phe
Coding: c.388G>T
MANE Select: NM_012186
dbSNP: rs1646884931
Type: single nucleotide variant
Location: chr1:47416703 (GRCh38)

Full FOXE3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital primary aphakia — 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/foxe3-p-val130phe (accessed [today's date]).

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