Is FOXI3 p.Ala72= (c.216C>A) pathogenic?

FOXI3 p.Ala72= (c.216C>A) is classified Likely benign in FOXI3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-21). Very rare (popmax 0.00353%, afr).

How common is FOXI3 p.Ala72= (c.216C>A) in the general population?

FOXI3 p.Ala72= (c.216C>A) is very rare (popmax 0.00353%, afr) (gnomAD).

FOXI3 p.Ala72=

c.216C>A · VCV3610447

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00353%, 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 0.15	GERP -1.3, phastCons 0.34
Overall
CADD	8.667	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00353% African / African-American · 2/56,582 alleles

Filtering AF 0.000586% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000219%

Overall 0.000204% 2/982,060 alleles · very rare exomes 0/836,020 · genomes 2/146,040 · 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.Ala72=
Coding: c.216C>A
MANE Select: NM_001135649
Type: single nucleotide variant
Location: chr2:88452320 (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.Ala72_Ala74del Uncertain significance ★ same residue
FOXI3 p.Ala72fs 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
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-ala72 (accessed [today's date]).

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