Is FOXI3 p.Pro85= (c.255C>A) pathogenic?

FOXI3 p.Pro85= (c.255C>A) is classified Likely benign in FOXI3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-14). Very rare (popmax 0.00177%, afr).

How common is FOXI3 p.Pro85= (c.255C>A) in the general population?

FOXI3 p.Pro85= (c.255C>A) is very rare (popmax 0.00177%, afr) (gnomAD).

FOXI3 p.Pro85=

c.255C>A · VCV3610589

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00177%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.85	GERP -3.4
Overall
CADD	9.371	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00177% African / African-American · 1/56,648 alleles

Overall 0.000102% 1/983,182 alleles · very rare exomes 0/837,034 · genomes 1/146,148 · 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: FOXI3
Protein: p.Pro85=
Coding: c.255C>A
MANE Select: NM_001135649
Type: single nucleotide variant
Location: chr2:88452281 (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.Pro85Ala Uncertain significance ★ ⚠ same residue
FOXI3 p.Pro85Arg Uncertain significance ★ ⚠ same residue
FOXI3 p.Pro85Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
FOXI3 p.Pro85_Gly86dup Uncertain significance ★ same residue
FOXI3 p.Pro85_Gly86insPro Uncertain significance ★ same residue
FOXI3 p.Pro85_Gly86insProPro Uncertain significance ★ same residue
FOXI3 p.Pro85dup Uncertain significance ★ same residue
FOXI3 p.Arg236Trp Likely pathogenic ★★ 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-pro85 (accessed [today's date]).

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