ARSA p.Gly394=
c.1182A>C · rs2146717672 · VCV1552980
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
metachromatic leukodystrophy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>A here scores Δ0.98 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.7 | GERP -3.5 |
| Overall | ||
| CADD | 5.465 | PHRED · no single calibrated threshold — expert panels disagree |
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
- ARSA
- Protein
- p.Gly394=
- Coding
- c.1182A>C
- MANE Select
- NM_000487
- dbSNP
- rs2146717672
- Type
- single nucleotide variant
- Location
- chr22:50625607 (GRCh38)
- Gene constraint
- LOEUF 1.166 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.43 · 10 PDB
- Residue 394
- a β-strand; a disulfide bond
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.Gly394Glu Uncertain significance ★ same residue
- ARSA c.1107+1G>A Pathogenic/Likely pathogenic ★★ same condition
- ARSA c.1107+1G>T Pathogenic ★★ same condition
- ARSA c.1108-2A>G Pathogenic ★★ same condition
- ARSA c.1108-3C>G Pathogenic/Likely pathogenic ★★ same condition
- ARSA c.1210+1G>A Pathogenic ★★ same condition
- ARSA c.224+1G>A Likely pathogenic ★★ same condition
- ARSA c.225-1G>C 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-gly394 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown