GBA2 p.Cys152=
c.456T>C · VCV3696090
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00538%, afr)
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 1.6 | GERP -1.5, phastCons 1 |
| Overall | ||
| CADD | 8.759 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00538%
African / African-American · 4/74,344 alleles
Filtering AF
0.00176%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00105%
Overall
0.000252%
4/1,584,946 alleles · very rare
exomes 2/1,432,784 · genomes 2/152,162 · 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.Cys152=
- Coding
- c.456T>C
- MANE Select
- NM_020944
- Type
- single nucleotide variant
- Location
- chr9:35744408 (GRCh38)
- Gene constraint
- LOEUF 0.773 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 89.77
- Residue 152
- 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-cys152 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown