Is FMO3 p.Val187fs (c.559del) pathogenic?

FMO3 p.Val187fs (c.559del) is classified Pathogenic/Likely pathogenic in FMO3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-22). Very rare (popmax 0.00446%, eas); Associated with trimethylaminuria.

What condition is associated with FMO3 p.Val187fs (c.559del)?

FMO3 p.Val187fs (c.559del) is associated with trimethylaminuria (ClinVar).

How common is FMO3 p.Val187fs (c.559del) in the general population?

FMO3 p.Val187fs (c.559del) is very rare (popmax 0.00446%, eas) (gnomAD).

FMO3 p.Val187fs

c.559del · rs1270775688 · VCV2822929

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

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 5 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.1	GERP -4

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,864 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000124% 2/1,613,976 alleles · very rare exomes 2/1,461,708 · genomes 0/152,268 · joint denominator

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: FMO3
Protein: p.Val187fs
Coding: c.559del
MANE Select: NM_001002294
dbSNP: rs1270775688
Type: Deletion
Location: chr1:171108153 (GRCh38)
Gene constraint: LOEUF 1.314 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.50

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.Val187Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
FMO3 p.Arg131fs Pathogenic/Likely pathogenic ★★ same condition
FMO3 p.Asn80fs Pathogenic/Likely pathogenic ★★ same condition
FMO3 p.Phe242fs Pathogenic/Likely pathogenic ★★ same condition
FMO3 p.Pro380fs Pathogenic/Likely pathogenic ★★ same condition
FMO3 p.Asn227fs Likely pathogenic ★ same condition
FMO3 p.Lys416fs Likely pathogenic ★ same condition
FMO3 p.Pro153fs 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-val187fs (accessed [today's date]).

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