GBA2 p.Pro465=
c.1395G>A · rs149501146 · VCV416640
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.481%, eas)
Conditions
2
Spastic paraplegia
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.46 | donor loss at this position · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.8 | GERP -3.8 |
| Overall | ||
| CADD | 0.242 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.481%
East Asian · 216/44,874 alleles
Filtering AF
0.429%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.408%
Overall
0.0193%
311/1,614,070 alleles · rare
exomes 261/1,461,798 · genomes 50/152,272 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.481% | 208 |
| Remaining individualsnot grpmax-eligible | 0.114% | 880 |
| Middle Eastern | 0.0165% | 6,062 |
| South Asian | 0.00329% | 30,354 |
| European (non-Finnish) | 0.00161% | 62,104 |
| African / African-American | 0.00133% | 75,038 |
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.Pro465=
- Coding
- c.1395G>A
- MANE Select
- NM_020944
- dbSNP
- rs149501146
- Type
- single nucleotide variant
- Location
- chr9:35740012 (GRCh38)
- Gene constraint
- LOEUF 0.773 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 89.77
- Residue 465
- a UniProt-annotated variant site (in spg46; loss of glucosylceramide catabolic process)
Similar variants
- GBA2 p.Pro465Leu Uncertain significance ★★ ⚠ same residue
- GBA2 p.Arg234Ter Pathogenic ★★ same condition
- GBA2 p.Arg340Ter Pathogenic ★★ same condition
- GBA2 p.Arg574Ter Pathogenic ★★ same condition
- GBA2 p.Arg630Trp Pathogenic/Likely pathogenic ★★ same condition
- GBA2 p.Arg873His Pathogenic/Likely pathogenic ★★ same condition
- GBA2 p.Ala187Thr Uncertain significance ★★ ⚠ same condition
- GBA2 p.Ala235Gly 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-pro465 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown