FOXE1 p.Pro330=
c.990C>T · VCV4821170
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.754%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -8.5 | GERP -3 |
| Overall | ||
| CADD | 4.39 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.754%
African / African-American · 566/75,024 alleles
Filtering AF
0.703%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.683%
Overall
0.0382%
610/1,597,590 alleles · rare
exomes 304/1,445,236 · genomes 306/152,354 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.754% | 133 |
| Remaining individualsnot grpmax-eligible | 0.029% | 3,454 |
| Admixed American | 0.0251% | 3,982 |
| South Asian | 0.0011% | 90,772 |
| European (non-Finnish) | 0.000848% | 117,897 |
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
- FOXE1
- Protein
- p.Pro330=
- Coding
- c.990C>T
- MANE Select
- NM_004473
- Type
- single nucleotide variant
- Location
- chr9:97854904 (GRCh38)
- Gene constraint
- LOEUF 1.926 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 62.02
Similar variants
- FOXE1 p.Ala118Val Uncertain significance ★★ ⚠ same type
- FOXE1 p.Ala206Thr Uncertain significance ★★ ⚠ same type
- FOXE1 p.Arg51Gly Uncertain significance ★★ ⚠ same type
- FOXE1 p.Gly334Ala Uncertain significance ★★ ⚠ same type
- FOXE1 p.Leu205Val Uncertain significance ★★ ⚠ same type
- FOXE1 p.Ser294Asn Uncertain significance ★★ ⚠ same type
- FOXE1 c.-131G>C Benign ★★ same type
- FOXE1 c.-156T>C Benign ★★ 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/foxe1-p-pro330 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown