FOXI1 p.Pro140=
c.420C>T · VCV4746376
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00314%, nfe)
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 -10 | GERP -4.1 |
| Overall | ||
| CADD | 9.645 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00314%
European (non-Finnish) · 37/1,179,798 alleles
Filtering AF
0.00231%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00202%
Overall
0.00235%
38/1,613,716 alleles · very rare
exomes 38/1,461,358 · genomes 0/152,358 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00314% | 31,886 |
| South Asian | 0.0011% | 91,028 |
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.Pro140=
- Coding
- c.420C>T
- MANE Select
- NM_012188
- Type
- single nucleotide variant
- Location
- chr5:170106377 (GRCh38)
- Gene constraint
- LOEUF 1.061 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.03
- Residue 140
- a DNA-binding region
Similar variants
- 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
- FOXI1 p.Asn344Asp 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-pro140 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown