Is FOXE3 p.Pro237= (c.711G>T) pathogenic?

FOXE3 p.Pro237= (c.711G>T) is classified Likely benign in FOXE3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-03-07). Ultra-rare (popmax 0.0289%, mid); Associated with anterior segment dysgenesis.

What condition is associated with FOXE3 p.Pro237= (c.711G>T)?

FOXE3 p.Pro237= (c.711G>T) is associated with anterior segment dysgenesis, congenital primary aphakia (ClinVar).

How common is FOXE3 p.Pro237= (c.711G>T) in the general population?

FOXE3 p.Pro237= (c.711G>T) is ultra-rare (popmax 0.0289%, mid) (gnomAD).

FOXE3 p.Pro237=

c.711G>T · rs1177501502 · VCV1094799

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0289%, mid)

Conditions

anterior segment dysgenesis

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 0.36	GERP -3.6, phastCons 0.24
Overall
CADD	10.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0289% Middle Eastern · 1/3,464 alleles

Filtering AF 0.00572% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00409%

Overall 0.000987% 13/1,317,628 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0289%	3,464
South Asian	0.0124%	8,085
Remaining individualsnot grpmax-eligible	0.00419%	23,842
European (non-Finnish)	0.00029%	344,442

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: FOXE3
Protein: p.Pro237=
Coding: c.711G>T
MANE Select: NM_012186
dbSNP: rs1177501502
Type: single nucleotide variant
Location: chr1:47417026 (GRCh38)
Gene constraint: LOEUF 1.935 · pLI 0.12 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.68

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

Disease context

anterior segment dysgenesis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital primary aphakia

Similar variants

FOXE3 p.Pro237Ser Uncertain significance ★ ⚠ same residue
FOXE3 p.Ala78Thr Pathogenic/Likely pathogenic ★★ same condition
FOXE3 p.Cys240Ter Pathogenic ★★ same condition
FOXE3 p.Gly49Ter Pathogenic/Likely pathogenic ★★ same condition
FOXE3 p.Ser211Ter Pathogenic/Likely pathogenic ★★ same condition
FOXE3 p.Ala170Thr Uncertain significance ★★ ⚠ same condition
FOXE3 p.Ala189Val Uncertain significance ★★ ⚠ same condition
FOXE3 p.Ala206Asp Uncertain significance ★★ ⚠ 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/foxe3-p-pro237 (accessed [today's date]).

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