FTO p.Cys104=
c.312C>T · rs149711762 · VCV1369795
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.04%, afr)
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 0.81 | GERP -2, phastCons 1 |
| Overall | ||
| CADD | 9.388 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.04%
African / African-American · 30/75,020 alleles
Filtering AF
0.0288%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0249%
Overall
0.00496%
80/1,614,140 alleles · ultra-rare
exomes 68/1,461,888 · genomes 12/152,252 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.04% | 2,501 |
| Remaining individualsnot grpmax-eligible | 0.0192% | 5,209 |
| Middle Eastern | 0.0165% | 6,062 |
| Admixed American | 0.00333% | 30,012 |
| European (non-Finnish) | 0.0028% | 35,758 |
| South Asian | 0.0022% | 45,540 |
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.Cys104=
- Coding
- c.312C>T
- MANE Select
- NM_001080432
- dbSNP
- rs149711762
- Type
- single nucleotide variant
- Location
- chr16:53826052 (GRCh38)
- Gene constraint
- LOEUF 0.924 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.33 · 28 PDB
- Residue 104
- the 'fe2og dioxygenase domain' region; a β-strand
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-cys104 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown