Is FOXE1 p.Arg151Pro (c.452G>C) pathogenic?

FOXE1 p.Arg151Pro (c.452G>C) is classified Uncertain significance in FOXE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-24). AlphaMissense: likely pathogenic (0.9847); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with FOXE1 p.Arg151Pro (c.452G>C)?

FOXE1 p.Arg151Pro (c.452G>C) is associated with Inborn genetic diseases (ClinVar).

How common is FOXE1 p.Arg151Pro (c.452G>C) in the general population?

FOXE1 p.Arg151Pro (c.452G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FOXE1 p.Arg151Pro (c.452G>C)?

AlphaMissense predicts likely pathogenic (score 0.9847) — an in-silico prediction, not a clinical call.

FOXE1 p.Arg151Pro

c.452G>C · VCV4259164

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9847 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9847	likely pathogenic
REVEL	0.732	pathogenic-leaning
SaProt	LLR -9.64	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 518 bp · p 0.21 · regional, not allelic
Overall
CADD	32.0	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: FOXE1
Protein: p.Arg151Pro
Coding: c.452G>C
MANE Select: NM_004473
Type: single nucleotide variant
Location: chr9:97854366 (GRCh38)
Gene constraint: LOEUF 1.926 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 62.02

Full FOXE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FOXE1 p.Ala118Val Uncertain significance ★★ ⚠ same condition
FOXE1 p.Ala206Thr Uncertain significance ★★ ⚠ same condition
FOXE1 p.Arg51Gly Uncertain significance ★★ ⚠ same condition
FOXE1 p.Gly334Ala Uncertain significance ★★ ⚠ same condition
FOXE1 p.Leu205Val Uncertain significance ★★ ⚠ same condition
FOXE1 p.Ala159Thr Uncertain significance ★ ⚠ same condition
FOXE1 p.Ala164Val Uncertain significance ★ ⚠ same condition
FOXE1 p.Ala171Thr 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/foxe1-p-arg151pro (accessed [today's date]).

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