Is ASPA p.Val278fs (c.831del) pathogenic?

ASPA p.Val278fs (c.831del) is classified Pathogenic in ASPA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-11-07). No gnomAD frequency available for this variant; Associated with Canavan disease.

What condition is associated with ASPA p.Val278fs (c.831del)?

ASPA p.Val278fs (c.831del) is associated with Canavan disease (ClinVar).

How common is ASPA p.Val278fs (c.831del) in the general population?

ASPA p.Val278fs (c.831del) is no gnomAD frequency available for this variant (gnomAD).

How is Canavan disease inherited?

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

ASPA p.Val278fs

c.831del · rs1555541304 · VCV556989

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Canavan disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.4	GERP 1.9, phastCons 0.92

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ASPA
Protein: p.Val278fs
Coding: c.831del
MANE Select: NM_001170698 · reported on NM_000049
dbSNP: rs1555541304
Type: Deletion
Location: chr17:3498976 (GRCh38)

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

Disease context

Canavan disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Canavan disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

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/aspa-p-val278fs (accessed [today's date]).

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