FOXI3 p.Pro112=
c.336C>A · rs1676061958 · VCV1918926
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00162%, 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 -0.58 | GERP -3.6, phastCons 0.003 |
| Overall | ||
| CADD | 9.274 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00162%
African / African-American · 1/61,714 alleles
Filtering AF
3.4e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.3e-05%
Overall
0.00025%
3/1,197,716 alleles · very rare
exomes 2/1,049,242 · genomes 1/148,474 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00162% | 61,714 |
| European (non-Finnish) | 0.000206% | 485,041 |
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.Pro112=
- Coding
- c.336C>A
- MANE Select
- NM_001135649
- dbSNP
- rs1676061958
- Type
- single nucleotide variant
- Location
- chr2:88452200 (GRCh38)
- Gene constraint
- LOEUF 0.73 · pLI 0.65 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.00
- Residue 112
- the 'disordered' 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-pro112 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown