FTO p.Arg316=
c.948G>A · rs756887326 · VCV2173124
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
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 -0.044 | GERP -4.9, phastCons 0.18 |
| Overall | ||
| CADD | 4.806 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,080 alleles
Filtering AF
0.000878%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000718%
Overall
0.0013%
21/1,612,892 alleles · ultra-rare
exomes 19/1,460,792 · genomes 2/152,100 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,080 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,550 |
| Admixed American | 0.00167% | 59,968 |
| European (non-Finnish) | 0.00144% | 69,367 |
| African / African-American | 0.00134% | 74,838 |
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.Arg316=
- Coding
- c.948G>A
- MANE Select
- NM_001080432
- dbSNP
- rs756887326
- Type
- single nucleotide variant
- Location
- chr16:53873838 (GRCh38)
- Gene constraint
- LOEUF 0.924 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.33 · 28 PDB
- Residue 316
- the 'fe2og dioxygenase domain' region; a binding site; a UniProt-annotated variant site (in gdfd; has no residual normal activity, impaired ability to demethylate n(6)-methyladenosine rnas (m6a) rnas); a β-strand
Similar variants
- FTO p.Arg316Gln Likely pathogenic ★ same residue
- FTO p.Arg316Trp Uncertain significance ★ ⚠ same residue
- 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
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-arg316 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown