Is FMN2 p.Trp366Ter (c.1097G>A) pathogenic?

FMN2 p.Trp366Ter (c.1097G>A) is classified Likely pathogenic in FMN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-22). Very rare (popmax 0.000267%, nfe).

How common is FMN2 p.Trp366Ter (c.1097G>A) in the general population?

FMN2 p.Trp366Ter (c.1097G>A) is very rare (popmax 0.000267%, nfe) (gnomAD).

FMN2 p.Trp366Ter

c.1097G>A · rs1445709911 · VCV2580492

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000267%, nfe)

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 1 of 18
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 1.6, phastCons 1
Overall
CADD	37.0	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 0.000267% European (non-Finnish) · 3/1,124,324 alleles

Filtering AF 7.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2e-05%

Overall 0.000201% 3/1,496,200 alleles · very rare exomes 3/1,344,380 · genomes 0/151,820 · 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: FMN2
Protein: p.Trp366Ter
Coding: c.1097G>A
MANE Select: NM_020066
dbSNP: rs1445709911
Type: single nucleotide variant
Location: chr1:240093206 (GRCh38)
Gene constraint: LOEUF 0.51 · pLI 0.51 (gnomAD)
Structure: AlphaFold pLDDT 51.48 · 2 PDB
Residue 366: the 'disordered' region

Full FMN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FMN2 p.Ile183Phe Likely pathogenic ★★ ⚠ same type
FMN2 p.Ala1691Val Uncertain significance ★★ ⚠ same type
FMN2 p.Ala367Val Uncertain significance ★★ ⚠ same type
FMN2 p.Ala508Val Uncertain significance ★★ ⚠ same type
FMN2 p.Asp352Tyr Uncertain significance ★★ ⚠ same type
FMN2 p.Gln192Leu Uncertain significance ★★ ⚠ same type
FMN2 p.Gln210Arg Uncertain significance ★★ ⚠ same type
FMN2 p.Gly244Ala Uncertain significance ★★ ⚠ 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/fmn2-p-trp366ter (accessed [today's date]).

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