Is GBA2 p.Lys55fs (c.164_165del) pathogenic?

GBA2 p.Lys55fs (c.164165del) is classified Conflicting classifications of pathogenicity in GBA2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-12-09). No gnomAD frequency available for this variant; Associated with Spastic paraplegia.

What condition is associated with GBA2 p.Lys55fs (c.164_165del)?

GBA2 p.Lys55fs (c.164_165del) is associated with Spastic paraplegia (ClinVar).

How common is GBA2 p.Lys55fs (c.164_165del) in the general population?

GBA2 p.Lys55fs (c.164_165del) is no gnomAD frequency available for this variant (gnomAD).

GBA2 p.Lys55fs

c.164_165del · rs1827116262 · VCV986271

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Spastic paraplegia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP 0.87, phastCons 0.028

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GBA2
Protein: p.Lys55fs
Coding: c.164_165del
MANE Select: NM_020944
dbSNP: rs1827116262
Type: Deletion
Location: chr9:35748540 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.77
Residue 55: the 'disordered' region

Full GBA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Spastic paraplegia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GBA2 p.Met510fs Pathogenic ★ same condition
GBA2 p.Trp551fs Pathogenic ★ same condition
GBA2 c.1129+11del Benign ★ same condition
GBA2 c.1130-15_1130-14del Likely benign ★ same condition
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

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-lys55fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown