FOXI1 p.Ser3=
c.9C>A · rs750881040 · VCV2170436
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, 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 0.37 | GERP 0.31, phastCons 0.99 |
| Overall | ||
| CADD | 7.836 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,068 alleles
Filtering AF
0.0194%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.016%
Overall
0.0134%
215/1,610,076 alleles · ultra-rare
exomes 195/1,457,928 · genomes 20/152,148 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,034 |
| Admixed American | 0.0301% | 3,324 |
| Remaining individualsnot grpmax-eligible | 0.0161% | 6,224 |
| European (non-Finnish) | 0.0152% | 6,577 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00678% | 14,744 |
| African / African-American | 0.00267% | 37,407 |
| Finnishnot grpmax-eligible | 0.00157% | 63,796 |
| South Asian | 0.0011% | 90,788 |
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
- FOXI1
- Protein
- p.Ser3=
- Coding
- c.9C>A
- MANE Select
- NM_012188
- dbSNP
- rs750881040
- Type
- single nucleotide variant
- Location
- chr5:170105966 (GRCh38)
- Gene constraint
- LOEUF 1.061 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.03
- Residue 3
- the 'disordered' region
Similar variants
- FOXI1 p.Ser3Phe Uncertain significance ★★ ⚠ same residue
- FOXI1 c.-18G>A Uncertain significance ★★ same type
- FOXI1 p.Ala255Thr Uncertain significance ★★ ⚠ same type
- FOXI1 p.Ala338Val Uncertain significance ★★ ⚠ same type
- FOXI1 p.Arg213Cys Uncertain significance ★★ ⚠ same type
- FOXI1 p.Arg213His Uncertain significance ★★ ⚠ same type
- FOXI1 p.Arg267Gln Uncertain significance ★★ ⚠ same type
- FOXI1 p.Arg267Trp 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/foxi1-p-ser3 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown