Is ASPA p.Tyr142= (c.426C>T) pathogenic?

ASPA p.Tyr142= (c.426C>T) is classified Likely benign in ASPA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-11). Very rare (popmax 0.000512%, nfe); Associated with Canavan disease.

What condition is associated with ASPA p.Tyr142= (c.426C>T)?

ASPA p.Tyr142= (c.426C>T) is associated with Canavan disease (ClinVar).

How common is ASPA p.Tyr142= (c.426C>T) in the general population?

ASPA p.Tyr142= (c.426C>T) is very rare (popmax 0.000512%, nfe) (gnomAD).

How is Canavan disease inherited?

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

ASPA p.Tyr142=

c.426C>T · rs1380839164 · VCV1113064

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000512%, nfe)

Conditions

Canavan disease

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 0.47	GERP -2.8, phastCons 1
Overall
CADD	3.987	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000512% European (non-Finnish) · 6/1,170,834 alleles

Filtering AF 0.000184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000121%

Overall 0.000414% 6/1,448,566 alleles · very rare

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.Tyr142=
Coding: c.426C>T
MANE Select: NM_000049
dbSNP: rs1380839164
Type: single nucleotide variant
Location: chr17:3481792 (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 142: 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.Tyr142Ter Pathogenic ★ same residue
ASPA c.236+2T>C Likely pathogenic ★★ same condition
ASPA c.237-1G>T Likely pathogenic ★★ same condition
ASPA c.237-2A>T Pathogenic/Likely pathogenic ★★ same condition
ASPA c.527-1G>A Likely pathogenic ★★ same condition
ASPA c.527-2A>C Likely pathogenic ★★ same condition
ASPA c.527-2A>G Likely pathogenic ★★ same condition
ASPA c.634+1G>T Pathogenic/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-tyr142 (accessed [today's date]).

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