Is ASPA p.Asp204fs (c.609del) pathogenic?

ASPA p.Asp204fs (c.609del) is classified Pathogenic/Likely pathogenic in ASPA (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-24). Absent from gnomAD; Associated with Canavan disease.

What condition is associated with ASPA p.Asp204fs (c.609del)?

ASPA p.Asp204fs (c.609del) is associated with Canavan disease (ClinVar).

How common is ASPA p.Asp204fs (c.609del) in the general population?

ASPA p.Asp204fs (c.609del) is absent from gnomAD (gnomAD).

How is Canavan disease inherited?

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

ASPA p.Asp204fs

c.609del · rs1597439149 · VCV813439

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 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	predicted	premature termination codon in exon 4 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1

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.Asp204fs
Coding: c.609del
MANE Select: NM_000049
dbSNP: rs1597439149
Type: Deletion
Location: chr17:3489316 (GRCh38)
Gene constraint: LOEUF 1.098 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.14 · 8 PDB
Residue 204: a UniProt-annotated variant site (in cand; 12% residual enzyme activity); an α-helix

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

Similar variants

ASPA p.Asp204His Pathogenic/Likely pathogenic ★★ same residue
ASPA p.Asp204= Likely benign ★ same residue
ASPA p.Cys152fs Pathogenic/Likely pathogenic ★★ same condition
ASPA p.Cys276fs Pathogenic/Likely pathogenic ★★ same condition
ASPA p.Gln12fs Pathogenic ★★ same condition
ASPA p.Glu129fs Pathogenic ★★ same condition
ASPA p.Ile11fs Pathogenic/Likely pathogenic ★★ same condition
ASPA p.Lys103fs 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-asp204fs (accessed [today's date]).

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