Is ASPA p.Lys144= (c.432G>A) pathogenic?

ASPA p.Lys144= (c.432G>A) is classified Likely pathogenic in ASPA (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-07-22). Very rare (popmax 0.00104%, nfe); Associated with Canavan Disease, Familial Form.

What condition is associated with ASPA p.Lys144= (c.432G>A)?

ASPA p.Lys144= (c.432G>A) is associated with Canavan Disease, Familial Form, Canavan disease (ClinVar).

How common is ASPA p.Lys144= (c.432G>A) in the general population?

ASPA p.Lys144= (c.432G>A) is very rare (popmax 0.00104%, nfe) (gnomAD).

ASPA p.Lys144=

c.432G>A · rs754087904 · VCV554976

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00104%, nfe)

Conditions

Canavan Disease, Familial Form

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.78	loss · gain 0.01 · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00104% European (non-Finnish) · 12/1,158,820 alleles

Filtering AF 0.000552% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000436%

Overall 0.00082% 13/1,586,074 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00163%	61,358
European (non-Finnish)grpmax	0.00104%	96,568

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys144=
Coding: c.432G>A
MANE Select: NM_001170698 · reported on NM_000049
dbSNP: rs754087904
Type: single nucleotide variant
Location: chr17:3481798 (GRCh38)

Full ASPA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Canavan Disease, Familial Form — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Canavan disease

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-lys144 (accessed [today's date]).

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