Is FTO p.Glu190Asp (c.570A>T) pathogenic?

FTO p.Glu190Asp (c.570A>T) is classified Uncertain significance in FTO (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-01). AlphaMissense: likely benign (0.099); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with FTO p.Glu190Asp (c.570A>T)?

FTO p.Glu190Asp (c.570A>T) is associated with Inborn genetic diseases (ClinVar).

How common is FTO p.Glu190Asp (c.570A>T) in the general population?

FTO p.Glu190Asp (c.570A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FTO p.Glu190Asp (c.570A>T)?

AlphaMissense predicts likely benign (score 0.099) — an in-silico prediction, not a clinical call.

FTO p.Glu190Asp

c.570A>T · VCV3280136

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.099 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.099	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -6.70	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.8	GERP -0.55, phastCons 0.93
Regional constraint	o/e 0.91	unconstrained · MANE · 408 kb · p 0.024 · regional, not allelic
Overall
CADD	14.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FTO
Protein: p.Glu190Asp
Coding: c.570A>T
MANE Select: NM_001080432
Type: single nucleotide variant
Location: chr16:53826310 (GRCh38)
Gene constraint: LOEUF 0.924 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.33 · 28 PDB
Residue 190: the 'fe2og dioxygenase domain' region; an α-helix

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 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
FTO p.Ile492Thr 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-glu190asp (accessed [today's date]).

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