FTO p.Ala311=
c.933C>T · rs757869301 · VCV1970899
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00329%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.27 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.92 | GERP -0.076, phastCons 1 |
| Overall | ||
| CADD | 13.91 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00329%
South Asian · 3/91,066 alleles
Filtering AF
0.00145%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00123%
Overall
0.00192%
31/1,612,836 alleles · very rare
exomes 28/1,460,828 · genomes 3/152,008 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00329% | 30,355 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,212 |
| East Asian | 0.00223% | 44,854 |
| European (non-Finnish) | 0.00212% | 47,170 |
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
- FTO
- Protein
- p.Ala311=
- Coding
- c.933C>T
- MANE Select
- NM_001080432
- dbSNP
- rs757869301
- Type
- single nucleotide variant
- Location
- chr16:53873823 (GRCh38)
- Gene constraint
- LOEUF 0.924 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.33 · 28 PDB
- Residue 311
- the 'fe2og dioxygenase domain' region
Similar variants
- FTO p.Ala311Ser Uncertain significance ★★ ⚠ same residue
- FTO c.1239+6T>C Uncertain significance ★★ same type
- FTO p.Ala286Val Uncertain significance ★★ ⚠ same type
- FTO p.Arg265Gly Uncertain significance ★★ ⚠ same type
- FTO p.Arg473Gln Uncertain significance ★★ ⚠ same type
- FTO p.Arg52Ter Uncertain significance ★★ same type
- FTO p.Arg80Gln Uncertain significance ★★ ⚠ same type
- FTO p.Arg80Trp 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/fto-p-ala311 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown