FTO p.Val374=
c.1122C>T · rs145529071 · VCV761019
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0667%, 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 -4.1 | GERP -4.6 |
| Overall | ||
| CADD | 0.438 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0667%
Admixed American · 40/60,014 alleles
Filtering AF
0.0502%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0446%
Overall
0.00551%
89/1,613,956 alleles · ultra-rare
exomes 53/1,461,700 · genomes 36/152,256 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0667% | 1,500 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,681 |
| European (non-Finnish) | 0.00305% | 32,775 |
| African / African-American | 0.00267% | 37,511 |
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.Val374=
- Coding
- c.1122C>T
- MANE Select
- NM_001080432
- dbSNP
- rs145529071
- Type
- single nucleotide variant
- Location
- chr16:53888834 (GRCh38)
- Gene constraint
- LOEUF 0.924 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.33 · 28 PDB
- Residue 374
- 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-val374 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown