Is FMN2 p.Pro1046= (c.3138A>T) pathogenic?

FMN2 p.Pro1046= (c.3138A>T) is classified Likely benign in FMN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-06-01). Rare (popmax 0.337%, sas); Associated with FMN2-related disorder.

What condition is associated with FMN2 p.Pro1046= (c.3138A>T)?

FMN2 p.Pro1046= (c.3138A>T) is associated with FMN2-related disorder (ClinVar).

How common is FMN2 p.Pro1046= (c.3138A>T) in the general population?

FMN2 p.Pro1046= (c.3138A>T) is rare (popmax 0.337%, sas) (gnomAD).

FMN2 p.Pro1046=

c.3138A>T · rs530821922 · VCV2640167

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.337%, sas)

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 -12	GERP -1
Overall
CADD	0.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.337% South Asian · 26/7,712 alleles

Filtering AF 0.236% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.202%

Overall 0.0824% 178/216,042 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.337%	297
Ashkenazi Jewishnot grpmax-eligible	0.26%	385
Middle Eastern	0.186%	538
Remaining individualsnot grpmax-eligible	0.132%	759
East Asian	0.111%	905
African / African-American	0.0951%	1,052
Admixed American	0.0863%	1,159
Finnishnot grpmax-eligible	0.0718%	1,393
European (non-Finnish)	0.065%	1,538

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.Pro1046=
Coding: c.3138A>T
MANE Select: NM_020066
dbSNP: rs530821922
Type: single nucleotide variant
Location: chr1:240207950 (GRCh38)
Gene constraint: LOEUF 0.51 · pLI 0.51 (gnomAD)
Structure: AlphaFold pLDDT 51.48 · 2 PDB
Residue 1046: 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-pro1046 (accessed [today's date]).

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