Is FMN2 p.Pro1011= (c.3033T>G) pathogenic?

FMN2 p.Pro1011= (c.3033T>G) is classified Likely benign in FMN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-03-01). Rare (popmax 0.563%, eas); Associated with FMN2-related disorder.

What condition is associated with FMN2 p.Pro1011= (c.3033T>G)?

FMN2 p.Pro1011= (c.3033T>G) is associated with FMN2-related disorder (ClinVar).

How common is FMN2 p.Pro1011= (c.3033T>G) in the general population?

FMN2 p.Pro1011= (c.3033T>G) is rare (popmax 0.563%, eas) (gnomAD).

FMN2 p.Pro1011=

c.3033T>G · rs71535326 · VCV2640155

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.563%, eas)

Conditions

FMN2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -2
Overall
CADD	0.912	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.563% East Asian · 22/3,906 alleles

Filtering AF 0.381% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.322%

Overall 0.103% 100/96,632 alleles · rare exomes 99/93,172 · genomes 1/3,460 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.563%	178
African / African-American	0.257%	389
Admixed American	0.136%	735
Remaining individualsnot grpmax-eligible	0.114%	876
South Asian	0.088%	1,136
European (non-Finnish)	0.0807%	1,239
Ashkenazi Jewishnot grpmax-eligible	0.0463%	2,158
Finnishnot grpmax-eligible	0.0409%	2,444

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.Pro1011=
Coding: c.3033T>G
MANE Select: NM_020066
dbSNP: rs71535326
Type: single nucleotide variant
Location: chr1:240207845 (GRCh38)
Gene constraint: LOEUF 0.51 · pLI 0.51 (gnomAD)
Structure: AlphaFold pLDDT 51.48 · 2 PDB
Residue 1011: 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-pro1011 (accessed [today's date]).

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