Is ASPA p.Glu293fs (c.876_879del) pathogenic?

ASPA p.Glu293fs (c.876879del) is classified Pathogenic/Likely pathogenic in ASPA (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-07-13). Very rare (popmax 0.00398%, nfe); Associated with Canavan Disease, Familial Form.

What condition is associated with ASPA p.Glu293fs (c.876_879del)?

ASPA p.Glu293fs (c.876_879del) is associated with Canavan Disease, Familial Form, Canavan disease (ClinVar).

How common is ASPA p.Glu293fs (c.876_879del) in the general population?

ASPA p.Glu293fs (c.876_879del) is very rare (popmax 0.00398%, nfe) (gnomAD).

ASPA p.Glu293fs

c.876_879del · rs766720790 · VCV371665

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00398%, nfe)

Conditions

Canavan Disease, Familial Form

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (6 of 6) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00398% European (non-Finnish) · 47/1,180,038 alleles

Filtering AF 0.00307% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00275%

Overall 0.00356% 52/1,461,886 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,837
European (non-Finnish)grpmax	0.00398%	25,107
African / African-American	0.00266%	37,527

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ASPA
Protein: p.Glu293fs
Coding: c.876_879del
MANE Select: NM_000049
dbSNP: rs766720790
Type: Microsatellite
Location: chr17:3499016 (GRCh38)
Gene constraint: LOEUF 1.098 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.14 · 8 PDB

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

Disease context

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

Also linked: Canavan disease

Similar variants

ASPA p.Glu293del Uncertain significance same residue
ASPA p.Glu293= Likely benign ★ same residue
ASPA c.634+5_634+8del Pathogenic ★ same condition
ASPA p.Leu126fs Likely pathogenic ★ same condition
ASPA p.Phe100fs Pathogenic ★ same condition
ASPA c.634+10_634+12del Likely benign ★ same condition
ASPA c.744+17_744+20del Likely benign ★ same condition
ASPA c.236+2T>C Likely pathogenic ★★ 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/aspa-p-glu293fs (accessed [today's date]).

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