Is FTO p.Asp348Val (c.1043A>T) pathogenic?

FTO p.Asp348Val (c.1043A>T) is classified Uncertain significance in FTO (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-30). AlphaMissense: likely benign (0.0913); Ultra-rare (popmax 0.056%, afr); Associated with Inborn genetic diseases.

What condition is associated with FTO p.Asp348Val (c.1043A>T)?

FTO p.Asp348Val (c.1043A>T) is associated with Inborn genetic diseases (ClinVar).

How common is FTO p.Asp348Val (c.1043A>T) in the general population?

FTO p.Asp348Val (c.1043A>T) is ultra-rare (popmax 0.056%, afr) (gnomAD).

What do computational predictors say about FTO p.Asp348Val (c.1043A>T)?

AlphaMissense predicts likely benign (score 0.0913) — an in-silico prediction, not a clinical call.

FTO p.Asp348Val

c.1043A>T · VCV4620415

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0913 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.056%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0913	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -6.96	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 1.4	GERP -2.6, phastCons 0.1
Regional constraint	o/e 0.91	unconstrained · MANE · 408 kb · p 0.024 · regional, not allelic
Overall
CADD	13.78	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

Grpmax group 0.056% African / African-American · 42/74,984 alleles

Filtering AF 0.0425% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0379%

Overall 0.00279% 45/1,613,874 alleles · ultra-rare exomes 20/1,461,748 · genomes 25/152,126 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.056%	1,785
Admixed American	0.00333%	29,996
Remaining individualsnot grpmax-eligible	0.0016%	62,504

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.Asp348Val
Coding: c.1043A>T
MANE Select: NM_001080432
Type: single nucleotide variant
Location: chr16:53879911 (GRCh38)
Gene constraint: LOEUF 0.924 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.33 · 28 PDB

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-asp348val (accessed [today's date]).

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