FOXI3 p.Pro146=
c.438G>A · rs765588871 · VCV2057304
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0666%, mid)
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 -1.1 | GERP -4.3, phastCons 0.001 |
| Overall | ||
| CADD | 13.14 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0666%
Middle Eastern · 4/6,006 alleles
Filtering AF
0.0227%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0136%
Overall
0.00462%
72/1,559,754 alleles · ultra-rare
exomes 67/1,407,728 · genomes 5/152,026 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0666% | 1,501 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0174% | 5,748 |
| Admixed American | 0.0136% | 7,368 |
| Remaining individualsnot grpmax-eligible | 0.00991% | 10,087 |
| European (non-Finnish) | 0.00417% | 24,007 |
| South Asian | 0.00235% | 42,508 |
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.Pro146=
- Coding
- c.438G>A
- MANE Select
- NM_001135649
- dbSNP
- rs765588871
- Type
- single nucleotide variant
- Location
- chr2:88452098 (GRCh38)
- Gene constraint
- LOEUF 0.73 · pLI 0.65 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.00
- Residue 146
- 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-pro146 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown