FOXO1 p.Pro18=
c.54C>T · rs542262788 · VCV2643778
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.128%, nfe)
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 0.11 | GERP -0.81, phastCons 0.87 |
| Overall | ||
| CADD | 10.48 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.128%
European (non-Finnish) · 1,421/1,110,880 alleles
Filtering AF
0.122%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.12%
Overall
0.102%
1,486/1,463,328 alleles · rare
exomes 1,356/1,311,400 · genomes 130/151,928 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.128% | 782 |
| Remaining individualsnot grpmax-eligible | 0.0588% | 1,702 |
| Finnishnot grpmax-eligible | 0.0392% | 2,549 |
| African / African-American | 0.0176% | 5,692 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00753% | 13,275 |
| Admixed American | 0.00237% | 42,148 |
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.Pro18=
- Coding
- c.54C>T
- MANE Select
- NM_002015
- dbSNP
- rs542262788
- Type
- single nucleotide variant
- Location
- chr13:40666159 (GRCh38)
- Gene constraint
- LOEUF 0.348 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 51.76 · 11 PDB
- Residue 18
- the 'disordered' region
Similar variants
- FOXO1 c.*1254G>A Benign ★★ same type
- FOXO1 p.Phe307= 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
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-pro18 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown