Is FMO3 p.Ala52fs (c.155_191delinsTCCATCACAGGACCATGC) pathogenic?

FMO3 p.Ala52fs (c.155191delinsTCCATCACAGGACCATGC) is classified Likely pathogenic in FMO3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-21). Associated with trimethylaminuria.

What condition is associated with FMO3 p.Ala52fs (c.155_191delinsTCCATCACAGGACCATGC)?

FMO3 p.Ala52fs (c.155_191delinsTCCATCACAGGACCATGC) is associated with trimethylaminuria (ClinVar).

FMO3 p.Ala52fs

c.155_191delinsTCCATCACAGGACCATGC · VCV3573938

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

trimethylaminuria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.78	GERP 2, phastCons 0.062

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: FMO3
Protein: p.Ala52fs
Coding: c.155_191delinsTCCATCACAGGACCATGC
MANE Select: NM_001002294
Type: Indel
Location: chr1:171103807 (GRCh38)
Gene constraint: LOEUF 1.314 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.50
Residue 52: a UniProt-annotated variant site (in tmau)

Full FMO3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

trimethylaminuria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FMO3 p.Ala52Thr Uncertain significance ★ ⚠ same residue
FMO3 p.Arg387Cys Likely pathogenic ★ same condition
FMO3 p.Phe109fs Likely pathogenic ★ same condition
FMO3 c.484+2T>G Likely pathogenic ★★ same condition
FMO3 c.828-2A>G Likely pathogenic ★★ same condition
FMO3 p.Arg131fs Pathogenic/Likely pathogenic ★★ same condition
FMO3 p.Arg223Gln Likely pathogenic ★★ same condition
FMO3 p.Arg223Trp Likely pathogenic ★★ 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/fmo3-p-ala52fs (accessed [today's date]).

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