ARSA p.Thr48fs
c.141del · VCV4850935
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
metachromatic leukodystrophy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 1 of 8 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 7.8 | GERP 2.2, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- ARSA
- Protein
- p.Thr48fs
- Coding
- c.141del
- MANE Select
- NM_000487
- Type
- Deletion
- Location
- chr22:50627639 (GRCh38)
- Gene constraint
- LOEUF 1.166 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.43 · 10 PDB
- Residue 48
- an α-helix
Disease context
metachromatic leukodystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Metachromatic leukodystrophy (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Adolescent, Adult, Childhood, Infancy
- Prevalence
- 1-9 / 100 000 (Europe)
Similar variants
- ARSA p.Thr48= Likely benign ★ same residue
- ARSA c.979_979+3del Pathogenic/Likely pathogenic ★★ same condition
- ARSA p.Ala12fs Pathogenic ★★ same condition
- ARSA p.Ala5fs Pathogenic ★★ same condition
- ARSA p.Arg21fs Pathogenic/Likely pathogenic ★★ same condition
- ARSA p.Arg82fs Pathogenic/Likely pathogenic ★★ same condition
- ARSA p.Asp37fs Pathogenic ★★ same condition
- ARSA p.Gly101fs 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/arsa-p-thr48fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown