Is FMO3 p.Glu65fs (c.192del) pathogenic?

FMO3 p.Glu65fs (c.192del) is classified Pathogenic in FMO3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2003-08-01). Very rare (popmax 0.00144%, nfe); Associated with trimethylaminuria.

What condition is associated with FMO3 p.Glu65fs (c.192del)?

FMO3 p.Glu65fs (c.192del) is associated with trimethylaminuria (ClinVar).

How common is FMO3 p.Glu65fs (c.192del) in the general population?

FMO3 p.Glu65fs (c.192del) is very rare (popmax 0.00144%, nfe) (gnomAD).

FMO3 p.Glu65fs

c.192del · rs1331111339 · VCV16317

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

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 -0.032	GERP 1.1, phastCons 0.7

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00144% European (non-Finnish) · 17/1,179,748 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000718%

Overall 0.00112% 18/1,613,728 alleles · very rare exomes 18/1,461,488 · genomes 0/152,240 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)grpmax	0.00144%	69,397

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu65fs
Coding: c.192del
MANE Select: NM_001002294
dbSNP: rs1331111339
Type: Deletion
Location: chr1:171103842 (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.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.Val187fs 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-glu65fs (accessed [today's date]).

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