Is FMN2 p.Pro1164= (c.3492A>T) pathogenic?

FMN2 p.Pro1164= (c.3492A>T) is classified Benign in FMN2 (ClinVar, Single submitter, 2 submitters; last evaluated 2018-09-20). Common (popmax 17.4%, sas) — too common for a highly-penetrant pathogenic allele.

FMN2 p.Pro1164=

Q: How common is FMN2 p.Pro1164= (c.3492A>T) in the general population?

FMN2 p.Pro1164= (c.3492A>T) is common (popmax 17.4%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3492A>T · rs778804893 · VCV1183879

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 17.4%, sas) — too common for a highly-penetrant pathogenic allele

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 -2.5
Overall
CADD	0.954	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 17.4% South Asian · 2,473/14,236 alleles

Filtering AF 16.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 16.6%

Overall 11.7% 15,013/128,030 alleles · common exomes 14,975/127,348 · genomes 38/682 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	25%	4
South Asiangrpmax	17.4%	6
Remaining individualsnot grpmax-eligible	15.5%	6
Middle Eastern	14.8%	7
African / African-American	13.3%	8
Ashkenazi Jewishnot grpmax-eligible	13.1%	8
European (non-Finnish)	12%	8
East Asian	11.7%	9
Admixed American	7.35%	14
Finnishnot grpmax-eligible	5.86%	17

Amish 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.Pro1164=
Coding: c.3492A>T
MANE Select: NM_020066
dbSNP: rs778804893
Type: single nucleotide variant
Location: chr1:240208304 (GRCh38)
Gene constraint: LOEUF 0.51 · pLI 0.51 (gnomAD)
Structure: AlphaFold pLDDT 51.48 · 2 PDB
Residue 1164: the fh1 domain; the 'disordered' region

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

Similar variants

FMN2 p.Ile183Phe Likely pathogenic ★★ ⚠ same type
FMN2 p.Ala1691Val Uncertain significance ★★ ⚠ same type
FMN2 p.Ala367Val Uncertain significance ★★ ⚠ same type
FMN2 p.Ala508Val Uncertain significance ★★ ⚠ same type
FMN2 p.Asp352Tyr Uncertain significance ★★ ⚠ same type
FMN2 p.Gln192Leu Uncertain significance ★★ ⚠ same type
FMN2 p.Gln210Arg Uncertain significance ★★ ⚠ same type
FMN2 p.Gly244Ala Uncertain significance ★★ ⚠ same type

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-pro1164 (accessed [today's date]).

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