FOXL2 p.Pro46=
c.138G>T · VCV4964480
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0022%, sas)
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 -3.8 | GERP -4 |
| Overall | ||
| CADD | 8.566 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0022%
South Asian · 2/91,018 alleles
Filtering AF
0.000365%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000137%
Overall
0.000187%
3/1,606,938 alleles · very rare
exomes 3/1,454,694 · genomes 0/152,244 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0022% | 45,509 |
| European (non-Finnish) | 8.48e-05% | 1,178,819 |
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.Pro46=
- Coding
- c.138G>T
- MANE Select
- NM_023067
- Type
- single nucleotide variant
- Location
- chr3:138946585 (GRCh38)
- Gene constraint
- LOEUF 1.913 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 61.89 · 2 PDB
- Residue 46
- the 'disordered' region
Similar variants
- FOXL2 p.Pro46fs 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
- FOXL2 p.Ser107Gly 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-pro46 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown