FOXI3 p.Pro278=
c.834C>A · rs377442746 · VCV1581356
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0945%, 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 -0.025 | GERP -2.1, phastCons 0.001 |
| Overall | ||
| CADD | 5.344 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0945%
African / African-American · 69/73,054 alleles
Filtering AF
0.0765%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.07%
Overall
0.00522%
81/1,551,608 alleles · ultra-rare
exomes 46/1,399,434 · genomes 35/152,174 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0945% | 1,059 |
| Remaining individualsnot grpmax-eligible | 0.00998% | 10,016 |
| Admixed American | 0.00981% | 10,197 |
| South Asian | 0.00119% | 84,066 |
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.Pro278=
- Coding
- c.834C>A
- MANE Select
- NM_001135649
- dbSNP
- rs377442746
- Type
- single nucleotide variant
- Location
- chr2:88448636 (GRCh38)
- Gene constraint
- LOEUF 0.73 · pLI 0.65 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.00
- Residue 278
- the 'disordered' region
Similar variants
- FOXI3 p.Pro278His 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
- FOXI3 p.Glu163Lys 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-pro278 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown