Is FOXE3 p.Pro17= (c.51T>C) pathogenic?

FOXE3 p.Pro17= (c.51T>C) is classified Benign/Likely benign in FOXE3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-02). Rare (popmax 0.932%, afr); Associated with anterior segment dysgenesis.

What condition is associated with FOXE3 p.Pro17= (c.51T>C)?

FOXE3 p.Pro17= (c.51T>C) is associated with anterior segment dysgenesis, congenital primary aphakia (ClinVar).

How common is FOXE3 p.Pro17= (c.51T>C) in the general population?

FOXE3 p.Pro17= (c.51T>C) is rare (popmax 0.932%, afr) (gnomAD).

FOXE3 p.Pro17=

c.51T>C · rs548368038 · VCV1127506

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.932%, afr)

Conditions

anterior segment dysgenesis

⚠ 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
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 -4.1	GERP -3.1
Overall
CADD	1.495	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.932% African / African-American · 621/66,602 alleles

Filtering AF 0.872% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.847%

Overall 0.0502% 684/1,361,562 alleles · rare exomes 286/1,210,522 · genomes 398/151,040 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.932%	107
Remaining individualsnot grpmax-eligible	0.0675%	1,481
Admixed American	0.0556%	1,799
Middle Eastern	0.0272%	3,674
South Asian	0.00499%	20,027
European (non-Finnish)	0.000381%	262,676

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.Pro17=
Coding: c.51T>C
MANE Select: NM_012186
dbSNP: rs548368038
Type: single nucleotide variant
Location: chr1:47416366 (GRCh38)

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

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-pro17 (accessed [today's date]).

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