Is FTO p.Thr6= (c.18T>C) pathogenic?

FTO p.Thr6= (c.18T>C) is classified Benign/Likely benign in FTO (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-28). Common (popmax 9.1%, afr) — too common for a highly-penetrant pathogenic allele.

FTO p.Thr6=

Q: How common is FTO p.Thr6= (c.18T>C) in the general population?

FTO p.Thr6= (c.18T>C) is common (popmax 9.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.18T>C · rs73609956 · VCV319677

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 9.1%, afr) — too common for a highly-penetrant pathogenic allele

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 -2	GERP -5.1
Overall
CADD	9.686	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.1% African / African-American · 6,654/73,138 alleles

Filtering AF 8.92% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.84%

Overall 0.488% 7,572/1,551,466 alleles · common exomes 3,625/1,399,174 · genomes 3,947/152,292 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.1%	11
Remaining individualsnot grpmax-eligible	0.632%	158
Admixed American	0.61%	164
Middle Eastern	0.401%	249
South Asian	0.0262%	3,820
European (non-Finnish)	0.0158%	6,336

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.Thr6=
Coding: c.18T>C
MANE Select: NM_001080432
dbSNP: rs73609956
Type: single nucleotide variant
Location: chr16:53704202 (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

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-thr6 (accessed [today's date]).

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