FOXI3 p.Pro223=
c.669G>A · rs772775131 · VCV2888327
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00958%, 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 -6 | GERP -4.3 |
| Overall | ||
| CADD | 2.064 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00958%
African / African-American · 7/73,046 alleles
Filtering AF
0.00447%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00315%
Overall
0.00342%
53/1,551,438 alleles · very rare
exomes 48/1,399,264 · genomes 5/152,174 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00958% | 10,435 |
| European (non-Finnish) | 0.00392% | 25,487 |
| South Asian | 0.00119% | 84,020 |
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.Pro223=
- Coding
- c.669G>A
- MANE Select
- NM_001135649
- dbSNP
- rs772775131
- Type
- single nucleotide variant
- Location
- chr2:88448801 (GRCh38)
- Gene constraint
- LOEUF 0.73 · pLI 0.65 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.00
- Residue 223
- a DNA-binding region
Similar variants
- 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
- FOXI3 p.Glu163Lys Uncertain significance ★★ ⚠ same type
- FOXI3 p.Gly38Ala 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-pro223 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown