Is FTO p.Val201Ile (c.601G>A) pathogenic?

FTO p.Val201Ile (c.601G>A) is classified Uncertain significance in FTO (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-15). AlphaMissense: likely benign (0.113); Ultra-rare (popmax 0.07%, nfe); Associated with lethal polymalformative syndrome, Boissel type.

What condition is associated with FTO p.Val201Ile (c.601G>A)?

FTO p.Val201Ile (c.601G>A) is associated with lethal polymalformative syndrome, Boissel type (ClinVar).

How common is FTO p.Val201Ile (c.601G>A) in the general population?

FTO p.Val201Ile (c.601G>A) is ultra-rare (popmax 0.07%, nfe) (gnomAD).

What do computational predictors say about FTO p.Val201Ile (c.601G>A)?

AlphaMissense predicts likely benign (score 0.113) — an in-silico prediction, not a clinical call.

FTO p.Val201Ile

c.601G>A · rs150450891 · VCV884924

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.113 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.07%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

lethal polymalformative syndrome, Boissel type

Computational evidence

Protein change
AlphaMissense	0.113	likely benign
REVEL	0.314	indeterminate
SaProt	LLR -6.17	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 0.8, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 408 kb · p 0.024 · regional, not allelic
Overall
CADD	18.54	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 0.07% European (non-Finnish) · 826/1,180,034 alleles

Filtering AF 0.066% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0644%

Overall 0.0546% 882/1,614,164 alleles · ultra-rare exomes 797/1,461,892 · genomes 85/152,272 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.07%	1,429
Ashkenazi Jewishnot grpmax-eligible	0.0574%	1,742
Remaining individualsnot grpmax-eligible	0.0352%	2,841
Middle Eastern	0.0165%	6,062
Admixed American	0.00833%	12,004
Finnishnot grpmax-eligible	0.00781%	12,805
African / African-American	0.004%	25,012
East Asian	0.00223%	44,876
South Asian	0.0022%	45,541

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.Val201Ile
Coding: c.601G>A
MANE Select: NM_001080432
dbSNP: rs150450891
Type: single nucleotide variant
Location: chr16:53826341 (GRCh38)
Gene constraint: LOEUF 0.924 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.33 · 28 PDB
Residue 201: the 'fe2og dioxygenase domain' region; a β-strand

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

Disease context

lethal polymalformative syndrome, Boissel type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FTO p.Ala286Val Uncertain significance ★★ ⚠ same condition
FTO p.Arg80Gln Uncertain significance ★★ ⚠ same condition
FTO p.Arg80Trp Uncertain significance ★★ ⚠ same condition
FTO p.Asn143Ser Uncertain significance ★★ ⚠ same condition
FTO p.His62Arg Uncertain significance ★★ ⚠ same condition
FTO p.Met400Val Uncertain significance ★★ ⚠ same condition
FTO p.Pro252Ser Uncertain significance ★★ ⚠ same condition
FTO p.Pro93Arg 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-val201ile (accessed [today's date]).

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