Is ASPA p.Asp204= (c.612T>C) pathogenic?

ASPA p.Asp204= (c.612T>C) is classified Likely benign in ASPA (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-05). Very rare (popmax 0.00333%, amr); Associated with Canavan disease.

What condition is associated with ASPA p.Asp204= (c.612T>C)?

ASPA p.Asp204= (c.612T>C) is associated with Canavan disease (ClinVar).

How common is ASPA p.Asp204= (c.612T>C) in the general population?

ASPA p.Asp204= (c.612T>C) is very rare (popmax 0.00333%, amr) (gnomAD).

How is Canavan disease inherited?

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

ASPA p.Asp204=

c.612T>C · rs767152579 · VCV1148353

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

Canavan disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.31	GERP 1.7, phastCons 1
Overall
CADD	8.287	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,000 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000248% 4/1,610,276 alleles · very rare exomes 4/1,457,986 · genomes 0/152,290 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,000
European (non-Finnish)	0.00017%	588,422

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.Asp204=
Coding: c.612T>C
MANE Select: NM_000049
dbSNP: rs767152579
Type: single nucleotide variant
Location: chr17:3489320 (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.Asp204fs Pathogenic/Likely 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

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-asp204 (accessed [today's date]).

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