Is FMN2 p.Pro748Ser (c.2242C>T) pathogenic?

FMN2 p.Pro748Ser (c.2242C>T) is classified Uncertain significance in FMN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-29). AlphaMissense: likely pathogenic (0.606); Ultra-rare (popmax 0.0735%, eas); Associated with Inborn genetic diseases.

What condition is associated with FMN2 p.Pro748Ser (c.2242C>T)?

FMN2 p.Pro748Ser (c.2242C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FMN2 p.Pro748Ser (c.2242C>T) in the general population?

FMN2 p.Pro748Ser (c.2242C>T) is ultra-rare (popmax 0.0735%, eas) (gnomAD).

What do computational predictors say about FMN2 p.Pro748Ser (c.2242C>T)?

AlphaMissense predicts likely pathogenic (score 0.606) — an in-silico prediction, not a clinical call.

FMN2 p.Pro748Ser

c.2242C>T · rs200439578 · VCV2518425

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.606 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0735%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.606	likely pathogenic
REVEL	0.397	indeterminate
SaProt	LLR -6.35	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 1.9, phastCons 0.97
Regional constraint	o/e 1.03	unconstrained · MANE · 84 kb · p 0.48 · regional, not allelic
Overall
CADD	20.4	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 0.0735% East Asian · 33/44,882 alleles

Filtering AF 0.0538% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.047%

Overall 0.00223% 36/1,613,978 alleles · ultra-rare exomes 31/1,461,832 · genomes 5/152,146 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0735%	1,360
Remaining individualsnot grpmax-eligible	0.0032%	31,236
African / African-American	0.00134%	74,898

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.Pro748Ser
Coding: c.2242C>T
MANE Select: NM_020066
dbSNP: rs200439578
Type: single nucleotide variant
Location: chr1:240207054 (GRCh38)
Gene constraint: LOEUF 0.51 · pLI 0.51 (gnomAD)
Structure: AlphaFold pLDDT 51.48 · 2 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FMN2 p.Ala367Val Uncertain significance ★★ ⚠ same condition
FMN2 p.Ala508Val Uncertain significance ★★ ⚠ same condition
FMN2 p.Asp352Tyr Uncertain significance ★★ ⚠ same condition
FMN2 p.Gly244Ala Uncertain significance ★★ ⚠ same condition
FMN2 p.Gly553Arg Uncertain significance ★★ ⚠ same condition
FMN2 p.Lys1681Arg Uncertain significance ★★ ⚠ same condition
FMN2 p.Pro1221Ser Uncertain significance ★★ ⚠ same condition
FMN2 p.Pro1228Leu Uncertain significance ★★ ⚠ 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-pro748ser (accessed [today's date]).

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