Is FMN2 p.Arg540Ter (c.1618C>T) pathogenic?

FMN2 p.Arg540Ter (c.1618C>T) is classified Pathogenic in FMN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-20). Very rare (popmax 8.47e-05%, nfe); Associated with intellectual disability, autosomal recessive 47.

What condition is associated with FMN2 p.Arg540Ter (c.1618C>T)?

FMN2 p.Arg540Ter (c.1618C>T) is associated with intellectual disability, autosomal recessive 47 (ClinVar).

How common is FMN2 p.Arg540Ter (c.1618C>T) in the general population?

FMN2 p.Arg540Ter (c.1618C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

FMN2 p.Arg540Ter

c.1618C>T · rs1247510585 · VCV1028639

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 8.47e-05%, nfe)

Conditions

intellectual disability, autosomal recessive 47

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 2 of 18
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.6	GERP -1.1, 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 8.47e-05% European (non-Finnish) · 1/1,179,956 alleles

Overall 6.84e-05% 1/1,461,752 alleles · very rare

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.Arg540Ter
Coding: c.1618C>T
MANE Select: NM_020066
dbSNP: rs1247510585
Type: single nucleotide variant
Location: chr1:240123181 (GRCh38)
Gene constraint: LOEUF 0.51 · pLI 0.51 (gnomAD)
Structure: AlphaFold pLDDT 51.48 · 2 PDB

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

Disease context

intellectual disability, autosomal recessive 47 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FMN2 p.Ile183Phe Likely pathogenic ★★ ⚠ same condition
FMN2 p.Asp352Tyr Uncertain significance ★★ ⚠ same condition
FMN2 p.Gln192Leu Uncertain significance ★★ ⚠ same condition
FMN2 p.Gln210Arg Uncertain significance ★★ ⚠ same condition
FMN2 p.Pro1044Leu Uncertain significance ★★ ⚠ same condition
FMN2 p.Pro1187Leu Uncertain significance ★★ ⚠ same condition
FMN2 p.Thr415Ile Uncertain significance ★★ ⚠ same condition
FMN2 p.Ala1072= 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/fmn2-p-arg540ter (accessed [today's date]).

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