FTO p.Lys391=
c.1173G>A · rs202178298 · VCV2178942
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0113%, nfe)
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 0.6 | GERP -2.9, phastCons 1 |
| Overall | ||
| CADD | 4.105 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0113%
European (non-Finnish) · 133/1,179,910 alleles
Filtering AF
0.00969%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00905%
Overall
0.00855%
138/1,613,942 alleles · ultra-rare
exomes 134/1,461,728 · genomes 4/152,214 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0113% | 8,872 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,622 |
| African / African-American | 0.00133% | 74,922 |
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.Lys391=
- Coding
- c.1173G>A
- MANE Select
- NM_001080432
- dbSNP
- rs202178298
- Type
- single nucleotide variant
- Location
- chr16:53888885 (GRCh38)
- Gene constraint
- LOEUF 0.924 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.33 · 28 PDB
- Residue 391
- an α-helix
Similar variants
- FTO c.1239+6T>C Uncertain significance ★★ same type
- FTO p.Ala286Val Uncertain significance ★★ ⚠ same type
- FTO p.Ala311Ser 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-lys391 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown