Is FOXA2 p.Arg152Pro (c.455G>C) pathogenic?

FOXA2 p.Arg152Pro (c.455G>C) is classified Uncertain significance in FOXA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). AlphaMissense: likely pathogenic (0.8334); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with FOXA2 p.Arg152Pro (c.455G>C)?

FOXA2 p.Arg152Pro (c.455G>C) is associated with Inborn genetic diseases (ClinVar).

How common is FOXA2 p.Arg152Pro (c.455G>C) in the general population?

FOXA2 p.Arg152Pro (c.455G>C) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about FOXA2 p.Arg152Pro (c.455G>C)?

AlphaMissense predicts likely pathogenic (score 0.8334) — an in-silico prediction, not a clinical call.

FOXA2 p.Arg152Pro

c.455G>C · VCV4620195

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8334 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8334	likely pathogenic
REVEL	0.371	indeterminate
SaProt	LLR -4.22	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.4, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 1,528 bp · p 0.00098 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R146P vs ClinVar R152P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,912 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.00105% 17/1,613,836 alleles · very rare exomes 12/1,461,764 · genomes 5/152,072 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,456
Remaining individualsnot grpmax-eligible	0.0016%	62,480
Finnishnot grpmax-eligible	0.00156%	63,990
European (non-Finnish)	0.0011%	90,766

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: FOXA2
Protein: p.Arg152Pro
Coding: c.455G>C
MANE Select: NM_021784
Type: single nucleotide variant
Location: chr20:22582787 (GRCh38)
Gene constraint: LOEUF 0.518 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 58.29 · 3 PDB

Full FOXA2 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

FOXA2 p.Ala92Val Uncertain significance ★★ ⚠ same condition
FOXA2 p.Glu373Asp Uncertain significance ★★ ⚠ same condition
FOXA2 p.Met108Ile Uncertain significance ★★ ⚠ same condition
FOXA2 p.Met52Thr Uncertain significance ★★ same condition
FOXA2 p.Pro358Gln Uncertain significance ★★ ⚠ same condition
FOXA2 p.Ser99Leu Uncertain significance ★★ ⚠ same condition
FOXA2 p.Ala102Glu Uncertain significance ★ ⚠ same condition
FOXA2 p.Ala106Glu 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/foxa2-p-arg152pro (accessed [today's date]).

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