Is FMN2 p.Pro1000= (c.3000G>T) pathogenic?

FMN2 p.Pro1000= (c.3000G>T) is classified Benign in FMN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-26). Common (popmax 27.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with FMN2-related disorder.

What condition is associated with FMN2 p.Pro1000= (c.3000G>T)?

FMN2 p.Pro1000= (c.3000G>T) is associated with FMN2-related disorder (ClinVar).

FMN2 p.Pro1000=

Q: How common is FMN2 p.Pro1000= (c.3000G>T) in the general population?

FMN2 p.Pro1000= (c.3000G>T) is common (popmax 27.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3000G>T · rs71646889 · VCV3056508

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 27.8%, eas) — too common for a highly-penetrant pathogenic allele

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 -16	GERP -1.6
Overall
CADD	1.34	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 27.8% East Asian · 2,782/10,018 alleles

Filtering AF 26.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 26.6%

Overall 15.7% 32,725/208,940 alleles · common exomes 32,459/204,016 · genomes 266/4,924 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	28.7%	3
East Asiangrpmax	27.8%	4
Middle Eastern	27.7%	4
African / African-American	21.4%	5
Remaining individualsnot grpmax-eligible	20.9%	5
Finnishnot grpmax-eligible	19.6%	5
South Asian	19.5%	5
European (non-Finnish)	13.4%	7
Admixed American	8.24%	12
Amishnot grpmax-eligible	2.27%	44

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro1000=
Coding: c.3000G>T
MANE Select: NM_020066
dbSNP: rs71646889
Type: single nucleotide variant
Location: chr1:240207812 (GRCh38)
Gene constraint: LOEUF 0.51 · pLI 0.51 (gnomAD)
Structure: AlphaFold pLDDT 51.48 · 2 PDB
Residue 1000: 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-pro1000 (accessed [today's date]).

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