Is FOXE1 p.Ala173Pro (c.517G>C) pathogenic?

FOXE1 p.Ala173Pro (c.517G>C) is classified Uncertain significance in FOXE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-03). AlphaMissense: likely benign (0.1053); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with FOXE1 p.Ala173Pro (c.517G>C)?

FOXE1 p.Ala173Pro (c.517G>C) is associated with Inborn genetic diseases (ClinVar).

How common is FOXE1 p.Ala173Pro (c.517G>C) in the general population?

FOXE1 p.Ala173Pro (c.517G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FOXE1 p.Ala173Pro (c.517G>C)?

AlphaMissense predicts likely benign (score 0.1053) — an in-silico prediction, not a clinical call.

FOXE1 p.Ala173Pro

c.517G>C · rs1223127008 · VCV2229740

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1053 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1053	likely benign
REVEL	0.325	indeterminate
SaProt	LLR -15.08	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP -0.14, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 518 bp · p 0.21 · regional, not allelic
Overall
CADD	18.26	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.Ala173Pro
Coding: c.517G>C
MANE Select: NM_004473
dbSNP: rs1223127008
Type: single nucleotide variant
Location: chr9:97854431 (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.Ala173Asp Uncertain significance ★ same residue
FOXE1 p.Ala173Thr Uncertain significance ★ ⚠ same residue
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

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-ala173pro (accessed [today's date]).

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