ARSA p.Arg145Pro
c.434G>C · VCV4585531
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.659 | pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.23 | donor loss · deltas |
| Pangolin | Δ0.32 | loss · gain 0.18 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 3.3 | GERP 2, phastCons 1 |
| Regional constraint | o/e 1.00 | unconstrained · MANE · 2,631 bp · p 0.96 · regional, not allelic |
| Overall | ||
| CADD | 27.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,179,562 alleles
Overall
6.85e-05%
1/1,460,534 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.Arg145Pro
- Coding
- c.434G>C
- MANE Select
- NM_000487
- Type
- single nucleotide variant
- Location
- chr22:50627197 (GRCh38)
- Gene constraint
- LOEUF 1.166 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.43 · 10 PDB
- Residue 145
- a β-strand
Similar variants
- ARSA p.Arg145Gly Pathogenic/Likely pathogenic ★★ same residue
- ARSA p.Arg145Ter Pathogenic/Likely pathogenic ★★ same residue
- ARSA p.Arg145Gln Conflicting classifications of pathogenicity ★ same residue
- ARSA p.Arg290His Pathogenic/Likely pathogenic ★★ same condition
- ARSA p.Gly327Ser Pathogenic/Likely pathogenic ★★ same condition
- ARSA p.Pro138Arg Pathogenic/Likely pathogenic ★★ same condition
- ARSA p.Arg216Cys Uncertain significance ★★ same condition
- ARSA p.Arg498Cys Uncertain significance ★★ 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-arg145pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown