Is FMN2 p.Pro947Arg (c.2840C>G) pathogenic?

FMN2 p.Pro947Arg (c.2840C>G) is classified Likely benign in FMN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-01). AlphaMissense: likely benign (0.1782); Ultra-rare (popmax 0.0391%, nfe).

How common is FMN2 p.Pro947Arg (c.2840C>G) in the general population?

FMN2 p.Pro947Arg (c.2840C>G) is ultra-rare (popmax 0.0391%, nfe) (gnomAD).

What do computational predictors say about FMN2 p.Pro947Arg (c.2840C>G)?

AlphaMissense predicts likely benign (score 0.1782) — an in-silico prediction, not a clinical call.

FMN2 p.Pro947Arg

c.2840C>G · rs201741828 · VCV3025502

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1782 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0391%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1782	likely benign
REVEL	0.234	benign-leaning
SaProt	LLR -12.58	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -0.71, phastCons 0.011
Regional constraint	o/e 1.03	unconstrained · MANE · 84 kb · p 0.48 · regional, not allelic
Overall
CADD	17.81	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

Grpmax group 0.0391% European (non-Finnish) · 401/1,025,644 alleles

Filtering AF 0.0359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0347%

Overall 0.0294% 412/1,402,598 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0391%	2,558
Remaining individualsnot grpmax-eligible	0.00918%	10,890
Ashkenazi Jewishnot grpmax-eligible	0.00415%	24,104
Admixed American	0.0038%	26,334
African / African-American	0.00322%	31,070
Finnishnot grpmax-eligible	0.00173%	57,858

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.Pro947Arg
Coding: c.2840C>G
MANE Select: NM_020066
dbSNP: rs201741828
Type: single nucleotide variant
Location: chr1:240207652 (GRCh38)
Gene constraint: LOEUF 0.51 · pLI 0.51 (gnomAD)
Structure: AlphaFold pLDDT 51.48 · 2 PDB
Residue 947: the fh1 domain; the 'disordered' region

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

Similar variants

FMN2 p.Pro947Leu Benign/Likely benign ★★ same residue
FMN2 p.Pro947= Likely benign ★ same residue
FMN2 p.Pro947fs Likely pathogenic ★ same residue
FMN2 p.Pro947_Pro958delinsLeu Uncertain significance ★ same residue
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

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-pro947arg (accessed [today's date]).

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