Is FMN2 p.Pro1207Ala (c.3619C>G) pathogenic?

FMN2 p.Pro1207Ala (c.3619C>G) is classified Likely benign in FMN2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-05-20). AlphaMissense: likely benign (0.1005); Rare (popmax 0.43%, afr); Associated with FMN2-related disorder.

What condition is associated with FMN2 p.Pro1207Ala (c.3619C>G)?

FMN2 p.Pro1207Ala (c.3619C>G) is associated with FMN2-related disorder (ClinVar).

How common is FMN2 p.Pro1207Ala (c.3619C>G) in the general population?

FMN2 p.Pro1207Ala (c.3619C>G) is rare (popmax 0.43%, afr) (gnomAD).

What do computational predictors say about FMN2 p.Pro1207Ala (c.3619C>G)?

AlphaMissense predicts likely benign (score 0.1005) — an in-silico prediction, not a clinical call.

FMN2 p.Pro1207Ala

c.3619C>G · rs145138533 · VCV3046257

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1005 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.43%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

FMN2-related disorder

Computational evidence

Protein change
AlphaMissense	0.1005	likely benign
REVEL	0.246	benign-leaning
SaProt	LLR -10.40	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 0.58	GERP 0.45, phastCons 0.006
Regional constraint	o/e 1.12	unconstrained · MANE · 50 kb · p 0.065 · regional, not allelic
Overall
CADD	14.9	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 0.43% African / African-American · 315/73,296 alleles

Filtering AF 0.391% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.375%

Overall 0.0213% 340/1,595,668 alleles · rare exomes 139/1,446,814 · genomes 201/148,854 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.43%	233
Middle Eastern	0.0333%	3,005
Remaining individualsnot grpmax-eligible	0.0178%	5,634
Admixed American	0.0135%	7,419
South Asian	0.00333%	30,041
European (non-Finnish)	8.57e-05%	1,166,805

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.Pro1207Ala
Coding: c.3619C>G
MANE Select: NM_020066
dbSNP: rs145138533
Type: single nucleotide variant
Location: chr1:240208431 (GRCh38)
Gene constraint: LOEUF 0.51 · pLI 0.51 (gnomAD)
Structure: AlphaFold pLDDT 51.48 · 2 PDB
Residue 1207: 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-pro1207ala (accessed [today's date]).

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