ARSA p.Gln155=
c.465G>A · rs199476377 · VCV166691
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
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/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.79 | donor loss · deltas |
|---|---|---|
| Pangolin | Δ0.65 | loss · gain 0.01 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 2, phastCons 1 |
| Overall | ||
| CADD | 19.0 | 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.Gln155=
- Coding
- c.465G>A
- MANE Select
- NM_000487
- dbSNP
- rs199476377
- Type
- single nucleotide variant
- Location
- chr22:50627166 (GRCh38)
- Gene constraint
- LOEUF 1.166 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.43 · 10 PDB
- Residue 155
- a β-strand; a UniProt-annotated variant site (in mld; juvenile-onset); a UniProt-annotated variant site (in mld)
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.Gln155Arg Likely pathogenic ★ same residue
- ARSA p.Gln155His 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
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-gln155 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown