ARSA p.Leu253Val
c.757C>G · rs771024706 · VCV3237233
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00133%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.684 | pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.9 | GERP -2.5, phastCons 1 |
| Regional constraint | o/e 1.00 | unconstrained · MANE · 2,631 bp · p 0.96 · regional, not allelic |
| Overall | ||
| CADD | 18.58 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00133%
African / African-American · 1/75,070 alleles
Overall
6.84e-05%
1/1,461,814 alleles · very rare
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
- ARSA
- Protein
- p.Leu253Val
- Coding
- c.757C>G
- MANE Select
- NM_000487
- dbSNP
- rs771024706
- Type
- single nucleotide variant
- Location
- chr22:50626688 (GRCh38)
- Gene constraint
- LOEUF 1.166 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.43 · 10 PDB
- Residue 253
- an α-helix; a UniProt-annotated variant site (in mld; late-infantile; decreased enzymatic activity)
Similar variants
- ARSA p.Leu253= Likely benign ★ same residue
- ARSA c.1107+1G>A Pathogenic/Likely pathogenic ★★ same type
- ARSA c.1107+1G>T Pathogenic ★★ same type
- ARSA c.1108-2A>G Pathogenic ★★ same type
- ARSA c.1108-3C>G Pathogenic/Likely pathogenic ★★ same type
- ARSA c.1210+1G>A Pathogenic ★★ same type
- ARSA c.224+1G>A Likely pathogenic ★★ same type
- ARSA c.225-1G>C Likely pathogenic ★★ same type
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-leu253val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown