Is FMO3 p.Glu305Ter (c.913G>T) pathogenic?

FMO3 p.Glu305Ter (c.913G>T) is classified Pathogenic in FMO3 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0904%, nfe); Associated with FMO3-related disorders.

What condition is associated with FMO3 p.Glu305Ter (c.913G>T)?

FMO3 p.Glu305Ter (c.913G>T) is associated with FMO3-related disorders, trimethylaminuria (ClinVar).

How common is FMO3 p.Glu305Ter (c.913G>T) in the general population?

FMO3 p.Glu305Ter (c.913G>T) is ultra-rare (popmax 0.0904%, nfe) (gnomAD).

FMO3 p.Glu305Ter

c.913G>T · rs61753344 · VCV16304

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0904%, nfe)

Conditions

FMO3-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 9
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.35	GERP -0.48, phastCons 0.001
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0904% European (non-Finnish) · 1,066/1,179,770 alleles

Filtering AF 0.0858% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.084%

Overall 0.0726% 1,172/1,613,774 alleles · ultra-rare exomes 1,118/1,461,502 · genomes 54/152,272 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.118%	844
European (non-Finnish)grpmax	0.0904%	1,107
Admixed American	0.0383%	2,609
African / African-American	0.00933%	10,717
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,594
Finnishnot grpmax-eligible	0.00156%	64,016

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.Glu305Ter
Coding: c.913G>T
MANE Select: NM_001002294
dbSNP: rs61753344
Type: single nucleotide variant
Location: chr1:171114092 (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

FMO3-related disorders

Also linked: trimethylaminuria

Similar variants

FMO3 c.484+2T>G Likely pathogenic ★★ same condition
FMO3 c.828-2A>G Likely pathogenic ★★ same condition
FMO3 p.Arg223Gln Likely pathogenic ★★ same condition
FMO3 p.Arg223Trp Likely pathogenic ★★ same condition
FMO3 p.Arg238Gln Pathogenic/Likely pathogenic ★★ same condition
FMO3 p.Arg238Ter Pathogenic/Likely pathogenic ★★ same condition
FMO3 p.Arg492Trp Pathogenic/Likely pathogenic ★★ same condition
FMO3 p.Arg500Ter Pathogenic/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-glu305ter (accessed [today's date]).

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