Is FMN2 p.Pro1044Arg (c.3131C>G) pathogenic?

FMN2 p.Pro1044Arg (c.3131C>G) is classified Uncertain significance in FMN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-09-01). AlphaMissense: likely benign (0.3079); Ultra-rare (popmax 0.0304%, sas).

How common is FMN2 p.Pro1044Arg (c.3131C>G) in the general population?

FMN2 p.Pro1044Arg (c.3131C>G) is ultra-rare (popmax 0.0304%, sas) (gnomAD).

What do computational predictors say about FMN2 p.Pro1044Arg (c.3131C>G)?

AlphaMissense predicts likely benign (score 0.3079) — an in-silico prediction, not a clinical call.

FMN2 p.Pro1044Arg

c.3131C>G · rs202165125 · VCV593938

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3079 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0304%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3079	likely benign
REVEL	0.192	benign-leaning
SaProt	LLR -11.51	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.15	GERP 0.56
Regional constraint	o/e 0.50	unconstrained · MANE · 399 bp · p 1.3e-07 · regional, not allelic
Overall
CADD	13.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0304% South Asian · 16/52,570 alleles

Filtering AF 0.019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0161%

Overall 0.0219% 155/707,758 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0448%	2,233
Ashkenazi Jewishnot grpmax-eligible	0.0378%	2,643
Remaining individualsnot grpmax-eligible	0.0368%	2,719
South Asiangrpmax	0.0304%	3,286
European (non-Finnish)	0.0208%	4,818
Admixed American	0.00361%	27,718

Finnish 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.Pro1044Arg
Coding: c.3131C>G
MANE Select: NM_020066
dbSNP: rs202165125
Type: single nucleotide variant
Location: chr1:240207943 (GRCh38)
Gene constraint: LOEUF 0.51 · pLI 0.51 (gnomAD)
Structure: AlphaFold pLDDT 51.48 · 2 PDB
Residue 1044: the fh1 domain; the 'disordered' region

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

Similar variants

FMN2 p.Pro1044Leu Uncertain significance ★★ ⚠ same residue
FMN2 p.Pro1044= Likely benign ★★ same residue
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

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-pro1044arg (accessed [today's date]).

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