Is FMN2 p.Ser295Pro (c.883T>C) pathogenic?

FMN2 p.Ser295Pro (c.883T>C) is classified Conflicting classifications of pathogenicity in FMN2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-10-24). AlphaMissense: likely benign (0.0886); Low-frequency (popmax 1.91%, afr).

How common is FMN2 p.Ser295Pro (c.883T>C) in the general population?

FMN2 p.Ser295Pro (c.883T>C) is low-frequency (popmax 1.91%, afr) (gnomAD).

What do computational predictors say about FMN2 p.Ser295Pro (c.883T>C)?

AlphaMissense predicts likely benign (score 0.0886) — an in-silico prediction, not a clinical call.

FMN2 p.Ser295Pro

c.883T>C · rs201538863 · VCV286882

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0886 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.91%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0886	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -6.24	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.24	GERP -2.7
Regional constraint	o/e 0.95	unconstrained · MANE · 31 kb · p 0.15 · regional, not allelic
Overall
CADD	8.568	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 1.91% African / African-American · 1,252/65,482 alleles

Filtering AF 1.82% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.79%

Overall 0.0979% 1,370/1,399,736 alleles · low-frequency exomes 577/1,247,884 · genomes 793/151,852 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.91%	52
Admixed American	0.142%	705
Remaining individualsnot grpmax-eligible	0.102%	979
Middle Eastern	0.0458%	2,182
South Asian	0.00317%	31,553
European (non-Finnish)	0.00157%	63,881

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.Ser295Pro
Coding: c.883T>C
MANE Select: NM_020066
dbSNP: rs201538863
Type: single nucleotide variant
Location: chr1:240092992 (GRCh38)
Gene constraint: LOEUF 0.51 · pLI 0.51 (gnomAD)
Structure: AlphaFold pLDDT 51.48 · 2 PDB
Residue 295: the 'disordered' region

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

Similar variants

FMN2 p.Ser295Phe Uncertain significance ★ ⚠ 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
FMN2 p.Gln210Arg 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-ser295pro (accessed [today's date]).

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