Is ASPA c.526+16del pathogenic?

ASPA c.526+16del is classified Likely benign in ASPA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-07). Very rare (popmax 0.00223%, eas); Associated with Canavan disease.

What condition is associated with ASPA c.526+16del?

ASPA c.526+16del is associated with Canavan disease (ClinVar).

How common is ASPA c.526+16del in the general population?

ASPA c.526+16del is very rare (popmax 0.00223%, eas) (gnomAD).

How is Canavan disease inherited?

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

ASPA c.526+16del

rs757010194 · VCV2989516

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

Canavan disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +16	near-intronic (+16 nt from the splice site)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.1	GERP 1.5, phastCons 0.41
Non-coding constraint	Z 3.84	1 kb window · o/e 0.69 · regional · uncalibrated
Overall
CADD	1.155	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,750 alleles

Overall 0.000126% 2/1,583,210 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,750
European (non-Finnish)	8.68e-05%	1,151,938

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
Coding: c.526+16del
MANE Select: NM_000049
dbSNP: rs757010194
Type: Deletion
Location: chr17:3483606 (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 — 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.Asp204fs Pathogenic/Likely pathogenic ★★ same condition
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
ASPA p.Met82fs 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-c-526-plus-16del (accessed [today's date]).

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