Is FMN2 p.Ser282Arg (c.846C>A) pathogenic?

FMN2 p.Ser282Arg (c.846C>A) is classified Uncertain significance in FMN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-03-16). AlphaMissense: ambiguous (0.4073); No allele count reported in gnomAD v4.1 (AN 1,419,650).

How common is FMN2 p.Ser282Arg (c.846C>A) in the general population?

FMN2 p.Ser282Arg (c.846C>A) is no allele count reported in gnomAD v4.1 (AN 1,419,650) (gnomAD).

What do computational predictors say about FMN2 p.Ser282Arg (c.846C>A)?

AlphaMissense predicts ambiguous (score 0.4073) — an in-silico prediction, not a clinical call.

FMN2 p.Ser282Arg

c.846C>A · rs886043509 · VCV286881

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4073 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,419,650)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4073	ambiguous
REVEL	0.066	moderately benign-leaning
SaProt	LLR -6.73	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.57	GERP 1.6, phastCons 0.002
Regional constraint	o/e 0.95	unconstrained · MANE · 31 kb · p 0.15 · regional, not allelic
Overall
CADD	18.36	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

No allele count reported in gnomAD v4.1 (AN 1,419,650). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FMN2
Protein: p.Ser282Arg
Coding: c.846C>A
MANE Select: NM_020066
dbSNP: rs886043509
Type: single nucleotide variant
Location: chr1:240092955 (GRCh38)
Gene constraint: LOEUF 0.51 · pLI 0.51 (gnomAD)
Structure: AlphaFold pLDDT 51.48 · 2 PDB
Residue 282: 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-ser282arg (accessed [today's date]).

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