Is FMO3 p.Ser57Ter (c.170C>G) pathogenic?

FMO3 p.Ser57Ter (c.170C>G) is classified Pathogenic in FMO3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-17). Very rare (popmax 0.0022%, sas).

How common is FMO3 p.Ser57Ter (c.170C>G) in the general population?

FMO3 p.Ser57Ter (c.170C>G) is very rare (popmax 0.0022%, sas) (gnomAD).

FMO3 p.Ser57Ter

c.170C>G · rs1655517675 · VCV2744460

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

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 3 of 9
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Pangolin	Δ0.23	loss · gain 0.13 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 4.7	GERP 1.8, phastCons 1
Overall
CADD	36.0	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 0.0022% South Asian · 2/91,088 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000136%

Overall 0.000124% 2/1,613,852 alleles · very rare exomes 2/1,461,628 · genomes 0/152,224 · joint denominator

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.Ser57Ter
Coding: c.170C>G
MANE Select: NM_001002294
dbSNP: rs1655517675
Type: single nucleotide variant
Location: chr1:171103822 (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

Similar variants

FMO3 c.484+2T>G Likely pathogenic ★★ same type
FMO3 c.828-2A>G Likely pathogenic ★★ same type
FMO3 p.Arg223Gln Likely pathogenic ★★ same type
FMO3 p.Arg223Trp Likely pathogenic ★★ same type
FMO3 p.Arg238Gln Pathogenic/Likely pathogenic ★★ same type
FMO3 p.Arg238Ter Pathogenic/Likely pathogenic ★★ same type
FMO3 p.Arg492Trp Pathogenic/Likely pathogenic ★★ same type
FMO3 p.Arg500Ter Pathogenic/Likely pathogenic ★★ same type

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-ser57ter (accessed [today's date]).

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