FOXO1 p.Phe307=
c.921T>C · rs45624735 · VCV708958
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.345%, amr)
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 -0.35 | GERP -3.6 |
| Overall | ||
| CADD | 5.686 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.345%
Admixed American · 207/60,032 alleles
Filtering AF
0.306%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.291%
Overall
0.157%
2,532/1,614,222 alleles · rare
exomes 2,323/1,461,890 · genomes 209/152,332 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.345% | 290 |
| Ashkenazi Jewishnot grpmax-eligible | 0.247% | 406 |
| Middle Eastern | 0.214% | 466 |
| Remaining individualsnot grpmax-eligible | 0.178% | 563 |
| European (non-Finnish) | 0.173% | 577 |
| South Asian | 0.0461% | 2,169 |
| African / African-American | 0.032% | 3,128 |
| Finnishnot grpmax-eligible | 0.0281% | 3,558 |
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
- FOXO1
- Protein
- p.Phe307=
- Coding
- c.921T>C
- MANE Select
- NM_002015
- dbSNP
- rs45624735
- Type
- single nucleotide variant
- Location
- chr13:40560570 (GRCh38)
- Gene constraint
- LOEUF 0.348 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 51.76 · 11 PDB
- Residue 307
- the 'disordered' region; the 'sufficient for interaction with nlk' region
Similar variants
- FOXO1 c.*1254G>A Benign ★★ same type
- FOXO1 p.Ser502= Benign ★★ same type
- FOXO1 p.Thr333= Benign/Likely benign ★★ same type
- FOXO1 p.Ala101Thr Uncertain significance ★ ⚠ same type
- FOXO1 p.Ala255Val Uncertain significance ★ ⚠ same type
- FOXO1 p.Ala356Thr Uncertain significance ★ ⚠ same type
- FOXO1 p.Ala511Ser Uncertain significance ★ ⚠ same type
- FOXO1 p.Ala533Ser 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/foxo1-p-phe307 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown