Is FOXI3 p.Arg332= (c.996G>T) pathogenic?

FOXI3 p.Arg332= (c.996G>T) is classified Likely benign in FOXI3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-18). Very rare (popmax 0.00489%, eas).

How common is FOXI3 p.Arg332= (c.996G>T) in the general population?

FOXI3 p.Arg332= (c.996G>T) is very rare (popmax 0.00489%, eas) (gnomAD).

FOXI3 p.Arg332=

c.996G>T · VCV3605070

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00489%, eas)

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 -1.9	GERP -3.4
Overall
CADD	0.41	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00489% East Asian · 2/40,922 alleles

Filtering AF 0.00081% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000303%

Overall 0.000322% 5/1,551,480 alleles · very rare exomes 4/1,399,398 · genomes 1/152,082 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00489%	20,461
European (non-Finnish)	0.000262%	382,329

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.Arg332=
Coding: c.996G>T
MANE Select: NM_001135649
Type: single nucleotide variant
Location: chr2:88448474 (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.Arg332Gln Uncertain significance ★ ⚠ same residue
FOXI3 p.Arg332Leu Uncertain significance ★ ⚠ same residue
FOXI3 p.Arg332Trp Uncertain significance ★ ⚠ 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

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-arg332 (accessed [today's date]).

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