Is FMN2 p.Pro969Arg (c.2906C>G) pathogenic?

FMN2 p.Pro969Arg (c.2906C>G) is classified Uncertain significance in FMN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-26). AlphaMissense: likely benign (0.1875); Very rare (popmax 0.0035%, amr); Associated with Inborn genetic diseases.

What condition is associated with FMN2 p.Pro969Arg (c.2906C>G)?

FMN2 p.Pro969Arg (c.2906C>G) is associated with Inborn genetic diseases (ClinVar).

How common is FMN2 p.Pro969Arg (c.2906C>G) in the general population?

FMN2 p.Pro969Arg (c.2906C>G) is very rare (popmax 0.0035%, amr) (gnomAD).

What do computational predictors say about FMN2 p.Pro969Arg (c.2906C>G)?

AlphaMissense predicts likely benign (score 0.1875) — an in-silico prediction, not a clinical call.

FMN2 p.Pro969Arg

c.2906C>G · rs753365434 · VCV2218071

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1875 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0035%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1875	likely benign
REVEL	0.197	benign-leaning
SaProt	LLR -12.87	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
Regional constraint	o/e 0.73	unconstrained · MANE · 222 bp · p 0.012 · regional, not allelic
Overall
CADD	15.86	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 0.0035% Admixed American · 2/57,078 alleles

Filtering AF 0.000581% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000218%

Overall 0.000135% 2/1,482,124 alleles · very rare exomes 2/1,339,120 · genomes 0/143,004 · 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.Pro969Arg
Coding: c.2906C>G
MANE Select: NM_020066
dbSNP: rs753365434
Type: single nucleotide variant
Location: chr1:240207718 (GRCh38)
Gene constraint: LOEUF 0.51 · pLI 0.51 (gnomAD)
Structure: AlphaFold pLDDT 51.48 · 2 PDB
Residue 969: the fh1 domain; the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FMN2 p.Pro969= Likely benign ★★ same residue
FMN2 p.Ala367Val Uncertain significance ★★ ⚠ same condition
FMN2 p.Ala508Val Uncertain significance ★★ ⚠ same condition
FMN2 p.Asp352Tyr Uncertain significance ★★ ⚠ same condition
FMN2 p.Gly244Ala Uncertain significance ★★ ⚠ same condition
FMN2 p.Gly553Arg Uncertain significance ★★ ⚠ same condition
FMN2 p.Lys1681Arg Uncertain significance ★★ ⚠ same condition
FMN2 p.Pro1221Ser Uncertain significance ★★ ⚠ 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-pro969arg (accessed [today's date]).

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