FOXL2 p.Ser217=
c.651C>T · VCV3716908
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.129%, 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 3 | GERP 2.2, phastCons 1 |
| Overall | ||
| CADD | 12.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.129%
African / African-American · 85/65,700 alleles
Filtering AF
0.107%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0989%
Overall
0.00796%
113/1,419,694 alleles · rare
exomes 44/1,267,816 · genomes 69/151,878 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.129% | 773 |
| Admixed American | 0.0418% | 2,394 |
| Remaining individualsnot grpmax-eligible | 0.0092% | 10,868 |
| East Asian | 0.003% | 33,284 |
| European (non-Finnish) | 0.000911% | 109,767 |
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
- FOXL2
- Protein
- p.Ser217=
- Coding
- c.651C>T
- MANE Select
- NM_023067
- Type
- single nucleotide variant
- Location
- chr3:138946072 (GRCh38)
- Gene constraint
- LOEUF 1.913 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 61.89 · 2 PDB
- Residue 217
- a UniProt-annotated variant site (in bpes; diffuse nuclear localization; normal transcriptional activation); a UniProt-annotated variant site (in bpes; diffuse nuclear localization; increased transactivation activity)
Similar variants
- FOXL2 p.Ser217Phe Pathogenic/Likely pathogenic ★★ same residue
- FOXL2 p.Ser217Cys Pathogenic ★ same residue
- FOXL2 p.Arg349Gly Likely pathogenic ★★ ⚠ same type
- FOXL2 p.Gln196Ter Pathogenic ★★ same type
- FOXL2 p.Gln219Ter Pathogenic ★★ same type
- FOXL2 p.Leu75Phe Pathogenic ★★ same type
- FOXL2 p.Met65Ile Likely pathogenic ★★ same type
- FOXL2 p.Met65Val Pathogenic/Likely pathogenic ★★ 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/foxl2-p-ser217 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown