FMO3 p.Val220=
c.660G>A · rs373775407 · VCV876847
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.012%, nfe)
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 -0.27 | GERP -2.7, phastCons 0.015 |
| Overall | ||
| CADD | 5.39 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.012%
European (non-Finnish) · 142/1,179,932 alleles
Filtering AF
0.0104%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0098%
Overall
0.00911%
147/1,613,874 alleles · ultra-rare
exomes 129/1,461,730 · genomes 18/152,144 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.012% | 8,309 |
| Finnishnot grpmax-eligible | 0.00625% | 16,009 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
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.Val220=
- Coding
- c.660G>A
- MANE Select
- NM_001002294
- dbSNP
- rs373775407
- Type
- single nucleotide variant
- Location
- chr1:171110830 (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-val220 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown