Is FMO3 p.Val236Ile (c.706G>A) pathogenic?

FMO3 p.Val236Ile (c.706G>A) is classified Benign/Likely benign in FMO3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-25). AlphaMissense: likely benign (0.0715); Rare (popmax 0.683%, sas); Associated with trimethylaminuria.

What condition is associated with FMO3 p.Val236Ile (c.706G>A)?

FMO3 p.Val236Ile (c.706G>A) is associated with trimethylaminuria (ClinVar).

How common is FMO3 p.Val236Ile (c.706G>A) in the general population?

FMO3 p.Val236Ile (c.706G>A) is rare (popmax 0.683%, sas) (gnomAD).

What do computational predictors say about FMO3 p.Val236Ile (c.706G>A)?

AlphaMissense predicts likely benign (score 0.0715) — an in-silico prediction, not a clinical call.

FMO3 p.Val236Ile

c.706G>A · rs201271626 · VCV293691

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0715 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.683%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

trimethylaminuria

Computational evidence

Protein change
AlphaMissense	0.0715	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -6.12	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -9.2	GERP -4
Regional constraint	o/e 1.04	unconstrained · MANE · 25 kb · p 0.27 · regional, not allelic
Overall
CADD	0.001	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.683% South Asian · 622/91,080 alleles

Filtering AF 0.639% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.621%

Overall 0.0427% 689/1,613,998 alleles · rare exomes 653/1,461,758 · genomes 36/152,240 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.683%	146
Middle Eastern	0.0495%	2,020
Remaining individualsnot grpmax-eligible	0.0432%	2,315
East Asian	0.0245%	4,079
African / African-American	0.00533%	18,756
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600
European (non-Finnish)	0.0017%	58,996
Finnishnot grpmax-eligible	0.00156%	64,040

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.Val236Ile
Coding: c.706G>A
MANE Select: NM_001002294
dbSNP: rs201271626
Type: single nucleotide variant
Location: chr1:171110876 (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 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-val236ile (accessed [today's date]).

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