ARSA p.Arg82Pro
c.245G>C · rs769892461 · VCV4847092
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000424%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.97 | strongly pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 2.2, phastCons 1 |
| Regional constraint | o/e 1.00 | unconstrained · MANE · 2,631 bp · p 0.96 · regional, not allelic |
| Overall | ||
| CADD | 32.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000424%
European (non-Finnish) · 5/1,178,734 alleles
Filtering AF
0.000124%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9e-05%
Overall
0.000344%
5/1,455,118 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.Arg82Pro
- Coding
- c.245G>C
- MANE Select
- NM_000487
- dbSNP
- rs769892461
- Type
- single nucleotide variant
- Location
- chr22:50627386 (GRCh38)
- Gene constraint
- LOEUF 1.166 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.43 · 10 PDB
- Residue 82
- an α-helix; a UniProt-annotated variant site (in mld; late-infantile-onset)
Similar variants
- ARSA p.Arg82Gln Pathogenic/Likely pathogenic ★★ same residue
- ARSA p.Arg82Trp Pathogenic/Likely pathogenic ★★ same residue
- ARSA p.Arg82Leu Pathogenic ★ same residue
- ARSA p.Arg82fs Pathogenic/Likely pathogenic ★★ 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
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-arg82pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown