Is FOXE3 p.Arg91= (c.273C>T) pathogenic?

FOXE3 p.Arg91= (c.273C>T) is classified Uncertain significance in FOXE3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-28). Very rare (popmax 8.5e-05%, nfe); Associated with anterior segment dysgenesis.

What condition is associated with FOXE3 p.Arg91= (c.273C>T)?

FOXE3 p.Arg91= (c.273C>T) is associated with anterior segment dysgenesis, congenital primary aphakia (ClinVar).

How common is FOXE3 p.Arg91= (c.273C>T) in the general population?

FOXE3 p.Arg91= (c.273C>T) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

FOXE3 p.Arg91=

c.273C>T · rs2521317088 · VCV2928673

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

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 -0.35	GERP -3.5, phastCons 0.19
Overall
CADD	10.65	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.5e-05% European (non-Finnish) · 1/1,176,748 alleles

Overall 6.22e-05% 1/1,607,208 alleles · very rare exomes 1/1,456,568 · genomes 0/150,640 · joint denominator

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.Arg91=
Coding: c.273C>T
MANE Select: NM_012186
dbSNP: rs2521317088
Type: single nucleotide variant
Location: chr1:47416588 (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-arg91 (accessed [today's date]).

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