Is VAPB c.*467G>A pathogenic?

VAPB c.467G>A is classified Likely benign in VAPB (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Rare (popmax 0.982%, afr); Associated with adult-onset proximal spinal muscular atrophy, autosomal dominant.

How common is VAPB c.*467G>A in the general population?

VAPB c.*467G>A is rare (popmax 0.982%, afr) (gnomAD).

VAPB c.*467G>A

Q: What condition is associated with VAPB c.*467G>A?

VAPB c.*467G>A is associated with adult-onset proximal spinal muscular atrophy, autosomal dominant, amyotrophic lateral sclerosis type 8 (ClinVar).

Q: How is Autosomal dominant adult-onset proximal spinal muscular atrophy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

rs141496875 · VCV896300

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.982%, afr)

Conditions

adult-onset proximal spinal muscular atrophy, autosomal dominant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.2	GERP -4.7
Non-coding constraint	Z 3.51	1 kb window · o/e 0.77 · regional · uncalibrated
Overall
CADD	0.387	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.982% African / African-American · 492/50,122 alleles

Filtering AF 0.91% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.882%

Overall 0.119% 541/454,414 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.982%	102
Remaining individualsnot grpmax-eligible	0.0742%	1,347
Admixed American	0.0329%	3,041
South Asian	0.0264%	3,793
East Asian	0.00695%	14,386
European (non-Finnish)	0.0022%	45,374

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: VAPB
Coding: c.*467G>A
MANE Select: NM_004738
dbSNP: rs141496875
Type: single nucleotide variant
Location: chr20:58444702 (GRCh38)
Gene constraint: LOEUF 0.699 · pLI 0.52 (gnomAD)
Structure: AlphaFold pLDDT 77.45 · 3 PDB

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

Disease context

adult-onset proximal spinal muscular atrophy, autosomal dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: amyotrophic lateral sclerosis type 8

For Autosomal dominant adult-onset proximal spinal muscular atrophy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

VAPB p.Pro56Ser Pathogenic ★★ same condition
VAPB p.Ala104Thr Uncertain significance ★★ ⚠ same condition
VAPB p.Arg182Lys Uncertain significance ★★ ⚠ same condition
VAPB p.Asp163Asn Uncertain significance ★★ ⚠ same condition
VAPB p.Asp24Asn Uncertain significance ★★ ⚠ same condition
VAPB p.Asp37Glu Uncertain significance ★★ ⚠ same condition
VAPB p.Asp62Asn Uncertain significance ★★ ⚠ same condition
VAPB p.Asp77Asn 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/vapb-c-star-467g-a (accessed [today's date]).

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