Is FTO p.Arg52Gln (c.155G>A) pathogenic?

FTO p.Arg52Gln (c.155G>A) is classified Uncertain significance in FTO (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-08). AlphaMissense: likely benign (0.1439); Very rare (popmax 0.00833%, amr); Associated with Inborn genetic diseases.

What condition is associated with FTO p.Arg52Gln (c.155G>A)?

FTO p.Arg52Gln (c.155G>A) is associated with Inborn genetic diseases (ClinVar).

How common is FTO p.Arg52Gln (c.155G>A) in the general population?

FTO p.Arg52Gln (c.155G>A) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about FTO p.Arg52Gln (c.155G>A)?

AlphaMissense predicts likely benign (score 0.1439) — an in-silico prediction, not a clinical call.

FTO p.Arg52Gln

c.155G>A · VCV4027219

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1439 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1439	likely benign
REVEL	0.374	indeterminate
SaProt	LLR -10.54	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 408 kb · p 0.024 · regional, not allelic
Overall
CADD	28.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00833% Admixed American · 5/59,992 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000806% 13/1,613,874 alleles · very rare exomes 8/1,461,774 · genomes 5/152,100 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	11,998
South Asian	0.00659%	15,178
Remaining individualsnot grpmax-eligible	0.0032%	31,238

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.Arg52Gln
Coding: c.155G>A
MANE Select: NM_001080432
Type: single nucleotide variant
Location: chr16:53825895 (GRCh38)
Gene constraint: LOEUF 0.924 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.33 · 28 PDB
Residue 52: the 'fe2og dioxygenase domain' region; a β-strand

Full FTO gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FTO p.Arg52Ter Uncertain significance ★★ same residue
FTO c.1239+6T>C Uncertain significance ★★ same condition
FTO p.Ala311Ser Uncertain significance ★★ ⚠ same condition
FTO p.Arg265Gly Uncertain significance ★★ ⚠ same condition
FTO p.Arg473Gln Uncertain significance ★★ ⚠ same condition
FTO p.Arg80Gln Uncertain significance ★★ ⚠ same condition
FTO p.Arg80Trp Uncertain significance ★★ ⚠ same condition
FTO p.Gln339His Uncertain significance ★★ ⚠ same condition

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-arg52gln (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown