Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 9 submitters
gnomAD v4.1
Common
common (popmax 44.2%, afr) — too common for a highly-penetrant pathogenic allele
Conditions
1
trimethylaminuria
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.6 | GERP -3.1 |
| Overall | ||
| CADD | 5.282 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
44.2%
African / African-American · 32,969/74,670 alleles
Filtering AF
43.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 43.6%
Overall
26.5%
426,599/1,607,532 alleles · common
exomes 379,031/1,455,540 · genomes 47,568/151,992 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 44.2% | 2 |
| East Asian | 37.4% | 3 |
| Admixed American | 36.7% | 3 |
| Finnishnot grpmax-eligible | 28.6% | 4 |
| Remaining individualsnot grpmax-eligible | 25.9% | 4 |
| Amishnot grpmax-eligible | 25.4% | 4 |
| European (non-Finnish) | 24.9% | 4 |
| South Asian | 23.3% | 4 |
| Ashkenazi Jewishnot grpmax-eligible | 19.1% | 5 |
| Middle Eastern | 14.8% | 7 |
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.Asn285=
- Coding
- c.855C>T
- MANE Select
- NM_001002294
- dbSNP
- rs909530
- Type
- single nucleotide variant
- Location
- chr1:171114034 (GRCh38)
- Gene constraint
- LOEUF 1.314 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 95.50
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-asn285 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown