Is FMO3 p.Ser17Phe (c.50C>T) pathogenic?

FMO3 p.Ser17Phe (c.50C>T) is classified Uncertain significance in FMO3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-12-04). AlphaMissense: likely pathogenic (0.8579); Absent from gnomAD v4.1; Associated with FMO3-related disorder.

What condition is associated with FMO3 p.Ser17Phe (c.50C>T)?

FMO3 p.Ser17Phe (c.50C>T) is associated with FMO3-related disorder (ClinVar).

How common is FMO3 p.Ser17Phe (c.50C>T) in the general population?

FMO3 p.Ser17Phe (c.50C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FMO3 p.Ser17Phe (c.50C>T)?

AlphaMissense predicts likely pathogenic (score 0.8579) — an in-silico prediction, not a clinical call.

FMO3 p.Ser17Phe

c.50C>T · rs2526256943 · VCV3029305

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8579 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

FMO3-related disorder

Computational evidence

Protein change
AlphaMissense	0.8579	likely pathogenic
REVEL	0.269	benign-leaning
SaProt	LLR -14.97	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.1	GERP 1.1, phastCons 0.81
Regional constraint	o/e 1.04	unconstrained · MANE · 25 kb · p 0.27 · regional, not allelic
Overall
CADD	24.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FMO3
Protein: p.Ser17Phe
Coding: c.50C>T
MANE Select: NM_001002294
dbSNP: rs2526256943
Type: single nucleotide variant
Location: chr1:171092708 (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 disorder

Similar variants

FMO3 p.Arg223Trp Likely pathogenic ★★ same condition
FMO3 p.Arg492Trp Pathogenic/Likely pathogenic ★★ same condition
FMO3 p.Glu305Ter Pathogenic ★★ same condition
FMO3 p.Pro153Leu Pathogenic/Likely pathogenic ★★ same condition
FMO3 p.Arg387Leu Conflicting classifications of pathogenicity ★ ⚠ same condition
FMO3 p.Asp408Tyr Conflicting classifications of pathogenicity ★ ⚠ same condition
FMO3 p.Gly475Asp Conflicting classifications of pathogenicity ★ ⚠ same condition
FMO3 c.133-2658A>T Likely benign 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-ser17phe (accessed [today's date]).

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