ARSA p.Pro138Arg
c.413C>G · rs74315462 · VCV986957
Pathogenic/Likely pathogenic
Multiple submitters
Classification
Pathogenic/Likely pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
2
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.971 | strongly pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2, phastCons 1 |
| Regional constraint | o/e 1.00 | unconstrained · MANE · 2,631 bp · p 0.96 · regional, not allelic |
| Overall | ||
| CADD | 24.5 | 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.Pro138Arg
- Coding
- c.413C>G
- MANE Select
- NM_000487
- dbSNP
- rs74315462
- Type
- single nucleotide variant
- Location
- chr22:50627218 (GRCh38)
- Gene constraint
- LOEUF 1.166 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.43 · 10 PDB
- Residue 138
- an α-helix; a UniProt-annotated variant site (in mld; significantly lower activity than wild-type protein)
Similar variants
- ARSA p.Pro138Leu Pathogenic ★★ same residue
- ARSA p.Pro138Ser Pathogenic ★★ same residue
- ARSA p.Pro138Ala Likely pathogenic ★ same residue
- ARSA p.Pro138Thr Pathogenic ★ same residue
- ARSA p.Pro138His Conflicting classifications of pathogenicity ★ same residue
- ARSA p.Pro138= Likely benign ★ same residue
- ARSA c.1107+1G>A Pathogenic/Likely pathogenic ★★ same condition
- ARSA c.1107+1G>T 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-pro138arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown