Is ASPA p.Ala202Pro (c.604G>C) pathogenic?

ASPA p.Ala202Pro (c.604G>C) is classified Likely pathogenic in ASPA (ClinVar, Single submitter, 1 submitter; last evaluated 2017-09-28). AlphaMissense: likely pathogenic (0.9734); Very rare (popmax 6.2e-05%); Associated with Canavan disease.

What condition is associated with ASPA p.Ala202Pro (c.604G>C)?

ASPA p.Ala202Pro (c.604G>C) is associated with Canavan disease (ClinVar).

How common is ASPA p.Ala202Pro (c.604G>C) in the general population?

ASPA p.Ala202Pro (c.604G>C) is very rare (popmax 6.2e-05%) (gnomAD).

How is Canavan disease inherited?

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

What do computational predictors say about ASPA p.Ala202Pro (c.604G>C)?

AlphaMissense predicts likely pathogenic (score 0.9734) — an in-silico prediction, not a clinical call.

ASPA p.Ala202Pro

c.604G>C · rs147763700 · VCV488070

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9734 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Canavan disease

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.9734	likely pathogenic ✓ concordant with ClinVar
REVEL	0.868	moderately pathogenic-leaning
SaProt	LLR -13.14	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 8.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 23 kb · p 0.0073 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,613,040 alleles · very rare exomes 1/1,460,796 · genomes 0/152,244 · joint denominator

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.Ala202Pro
Coding: c.604G>C
MANE Select: NM_000049
dbSNP: rs147763700
Type: single nucleotide variant
Location: chr17:3489312 (GRCh38)

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

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-ala202pro (accessed [today's date]).

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