GBA2 p.Arg587=
c.1761G>A · rs1041243651 · VCV2920079
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
Conditions
1
Spastic paraplegia
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.8 | GERP -1.5, phastCons 1 |
| Overall | ||
| CADD | 11.28 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,179,746 alleles
Overall
6.84e-05%
1/1,461,490 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
- GBA2
- Protein
- p.Arg587=
- Coding
- c.1761G>A
- MANE Select
- NM_020944
- dbSNP
- rs1041243651
- Type
- single nucleotide variant
- Location
- chr9:35739036 (GRCh38)
- Gene constraint
- LOEUF 0.773 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 89.77
- Residue 587
- a UniProt-annotated variant site (in spg46; loss of glucosylceramide catabolic process)
Similar variants
- GBA2 p.Arg234Ter Pathogenic ★★ same condition
- GBA2 p.Arg340Ter Pathogenic ★★ same condition
- GBA2 p.Arg574Ter Pathogenic ★★ same condition
- GBA2 p.Ala187Thr Uncertain significance ★★ ⚠ same condition
- GBA2 p.Arg215His Uncertain significance ★★ ⚠ same condition
- GBA2 p.Arg514Cys Uncertain significance ★★ ⚠ same condition
- GBA2 p.Arg575Gln Uncertain significance ★★ ⚠ same condition
- GBA2 p.Arg575Trp 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/gba2-p-arg587 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown