Is VAPB p.Asp116= (c.348T>C) pathogenic?

VAPB p.Asp116= (c.348T>C) is classified Likely benign in VAPB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-25). Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

How common is VAPB p.Asp116= (c.348T>C) in the general population?

VAPB p.Asp116= (c.348T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

VAPB p.Asp116=

Q: What condition is associated with VAPB p.Asp116= (c.348T>C)?

VAPB p.Asp116= (c.348T>C) is associated with Inborn genetic diseases, adult-onset proximal spinal muscular atrophy, autosomal dominant, amyotrophic lateral sclerosis type 8 (ClinVar).

c.348T>C · rs751762415 · VCV465873

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

Inborn genetic diseases

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 6.2	GERP 0.6, phastCons 1
Overall
CADD	11.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,926 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.00062% 10/1,613,864 alleles · very rare exomes 8/1,461,648 · genomes 2/152,216 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,926
European (non-Finnish)	0.000763%	131,111

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
Protein: p.Asp116=
Coding: c.348T>C
MANE Select: NM_004738
dbSNP: rs751762415
Type: single nucleotide variant
Location: chr20:58438977 (GRCh38)
Gene constraint: LOEUF 0.699 · pLI 0.52 (gnomAD)
Structure: AlphaFold pLDDT 77.45 · 3 PDB
Residue 116: a β-strand; the msp domain

Full VAPB 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

Also linked: adult-onset proximal spinal muscular atrophy, autosomal dominant amyotrophic lateral sclerosis type 8

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-p-asp116 (accessed [today's date]).

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