Is FMN2 p.Ala508Val (c.1523C>T) pathogenic?

FMN2 p.Ala508Val (c.1523C>T) is classified Uncertain significance in FMN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-08). AlphaMissense: likely benign (0.1316); Very rare (popmax 0.00553%, eas); Associated with Inborn genetic diseases.

What condition is associated with FMN2 p.Ala508Val (c.1523C>T)?

FMN2 p.Ala508Val (c.1523C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FMN2 p.Ala508Val (c.1523C>T) in the general population?

FMN2 p.Ala508Val (c.1523C>T) is very rare (popmax 0.00553%, eas) (gnomAD).

What do computational predictors say about FMN2 p.Ala508Val (c.1523C>T)?

AlphaMissense predicts likely benign (score 0.1316) — an in-silico prediction, not a clinical call.

FMN2 p.Ala508Val

c.1523C>T · rs376836605 · VCV3095810

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1316 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00553%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1316	likely benign
REVEL	0.152	moderately benign-leaning
SaProt	LLR -6.87	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.6	GERP 0.7, phastCons 0.041
Regional constraint	o/e 0.95	unconstrained · MANE · 31 kb · p 0.15 · regional, not allelic
Overall
CADD	14.99	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00553% East Asian · 2/36,180 alleles

Filtering AF 0.000916% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000343%

Overall 0.000352% 5/1,420,014 alleles · very rare exomes 4/1,267,942 · genomes 1/152,072 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00553%	18,090
Remaining individualsnot grpmax-eligible	0.00551%	18,161

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.Ala508Val
Coding: c.1523C>T
MANE Select: NM_020066
dbSNP: rs376836605
Type: single nucleotide variant
Location: chr1:240093632 (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

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FMN2 p.Pro1221Ser Uncertain significance ★★ ⚠ same condition
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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-ala508val (accessed [today's date]).

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