GBA2 p.Pro598=
c.1794A>C · rs1401792284 · VCV509047
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00134%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.80 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.77 | gain · loss 0.62 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 2.3 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 23.6 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00134%
African / African-American · 1/74,854 alleles
Overall
6.21e-05%
1/1,610,044 alleles · very rare
exomes 0/1,457,850 · genomes 1/152,194 · joint denominator
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.Pro598=
- Coding
- c.1794A>C
- MANE Select
- NM_020944
- dbSNP
- rs1401792284
- Type
- single nucleotide variant
- Location
- chr9:35739003 (GRCh38)
- Gene constraint
- LOEUF 0.773 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 89.77
- Residue 598
- a UniProt-annotated variant site (in spg46; loss of glucosylceramide catabolic process)
Similar variants
- GBA2 c.1582+2T>G Likely pathogenic ★★ same type
- GBA2 p.Arg234Ter Pathogenic ★★ same type
- GBA2 p.Arg340Ter Pathogenic ★★ same type
- GBA2 p.Arg574Ter Pathogenic ★★ same type
- GBA2 p.Arg630Trp Pathogenic/Likely pathogenic ★★ same type
- GBA2 p.Arg870Ter Likely pathogenic ★★ same type
- GBA2 p.Arg873His Pathogenic/Likely pathogenic ★★ same type
- GBA2 p.Ala187Thr Uncertain significance ★★ ⚠ 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/gba2-p-pro598 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown