Is FOXI3 p.Ala69Pro (c.205G>C) pathogenic?

FOXI3 p.Ala69Pro (c.205G>C) is classified Uncertain significance in FOXI3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-17). AlphaMissense: likely benign (0.0929); Absent from gnomAD v4.1.

How common is FOXI3 p.Ala69Pro (c.205G>C) in the general population?

FOXI3 p.Ala69Pro (c.205G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FOXI3 p.Ala69Pro (c.205G>C)?

AlphaMissense predicts likely benign (score 0.0929) — an in-silico prediction, not a clinical call.

FOXI3 p.Ala69Pro

c.205G>C · rs2528917568 · VCV2037402

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0929 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.0929	likely benign
SaProt	LLR -10.73	damaging
⇒ SaProt calls this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.057	GERP -2.7, phastCons 0.003
Regional constraint	o/e 0.91	unconstrained · MANE · 563 bp · p 0.17 · regional, not allelic
Overall
CADD	16.25	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; SaProt is an independent agreement signal.

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: FOXI3
Protein: p.Ala69Pro
Coding: c.205G>C
MANE Select: NM_001135649
dbSNP: rs2528917568
Type: single nucleotide variant
Location: chr2:88452331 (GRCh38)
Gene constraint: LOEUF 0.73 · pLI 0.65 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 59.00

Full FOXI3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FOXI3 p.Ala69Val Uncertain significance ★ ⚠ same residue
FOXI3 p.Ala69= Likely benign ★ same residue
FOXI3 p.Arg236Trp Likely pathogenic ★★ same type
FOXI3 p.Ala71Pro Uncertain significance ★★ ⚠ same type
FOXI3 p.Arg238Ter Uncertain significance ★★ same type
FOXI3 p.Arg241Cys Uncertain significance ★★ ⚠ same type
FOXI3 p.Asp212Glu Uncertain significance ★★ ⚠ same type
FOXI3 p.Cys5Tyr Uncertain significance ★★ ⚠ same type

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/foxi3-p-ala69pro (accessed [today's date]).

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