Is FMN2 p.Pro1012= (c.3036C>G) pathogenic?

FMN2 p.Pro1012= (c.3036C>G) is classified Likely benign in FMN2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-08). Ultra-rare (popmax 0.0825%, nfe); Associated with FMN2-related disorder.

What condition is associated with FMN2 p.Pro1012= (c.3036C>G)?

FMN2 p.Pro1012= (c.3036C>G) is associated with FMN2-related disorder (ClinVar).

How common is FMN2 p.Pro1012= (c.3036C>G) in the general population?

FMN2 p.Pro1012= (c.3036C>G) is ultra-rare (popmax 0.0825%, nfe) (gnomAD).

FMN2 p.Pro1012=

c.3036C>G · rs201918371 · VCV2640156

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0825%, nfe)

Conditions

FMN2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -2
Overall
CADD	1.827	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0825% European (non-Finnish) · 187/226,700 alleles

Filtering AF 0.0728% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0691%

Overall 0.0564% 221/392,088 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0825%	1,212
Middle Eastern	0.07%	1,428
Remaining individualsnot grpmax-eligible	0.0484%	2,067
Finnishnot grpmax-eligible	0.0469%	2,131
African / African-American	0.0147%	6,798
Ashkenazi Jewishnot grpmax-eligible	0.0112%	8,936
Admixed American	0.00526%	18,998
South Asian	0.00229%	43,730

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.Pro1012=
Coding: c.3036C>G
MANE Select: NM_020066
dbSNP: rs201918371
Type: single nucleotide variant
Location: chr1:240207848 (GRCh38)
Gene constraint: LOEUF 0.51 · pLI 0.51 (gnomAD)
Structure: AlphaFold pLDDT 51.48 · 2 PDB
Residue 1012: the fh1 domain; the 'disordered' region

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

Disease context

FMN2-related disorder

Similar variants

FMN2 p.Ala951= Likely benign ★★ same condition
FMN2 p.Ala973= Benign/Likely benign ★★ same condition
FMN2 p.Gly1005= Likely benign ★★ same condition
FMN2 p.Gly1007= Likely benign ★★ same condition
FMN2 p.Gly1062= Likely benign ★★ same condition
FMN2 p.Gly941= Likely benign ★★ same condition
FMN2 p.Leu1058= Likely benign ★★ same condition
FMN2 p.Leu1069= Likely 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-pro1012 (accessed [today's date]).

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