ASPA c.237-2A>C
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
canonical splice-site (±1/±2)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Canavan disease
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | canonical splice-site (±1/±2) | predicted loss-of-function |
|---|---|---|
| Splicing | ||
| Splice region | acceptor -2 | canonical splice dinucleotide (acceptor -2) · inside the BP7-excluded zone |
| SpliceAI | Δ0.97 | acceptor loss · deltas |
| Pangolin | Δ0.87 | loss · gain 0.73 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.9, phastCons 1 |
| Non-coding constraint | Z 2.51 | 1 kb window · o/e 0.82 · regional · uncalibrated |
| Overall | ||
| CADD | 33.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- ASPA
- Coding
- c.237-2A>C
- MANE Select
- NM_000049
- Type
- single nucleotide variant
- Location
- chr17:3481601 (GRCh38)
- Gene constraint
- LOEUF 1.098 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 96.14 · 8 PDB
Disease context
Canavan disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Canavan disease (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Childhood, Infancy, Neonatal
Similar variants
- 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
- ASPA c.635-1G>C 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-c-237-minus-2a-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown