Is GLB1 p.Val164fs (c.488dup) pathogenic?

GLB1 p.Val164fs (c.488dup) is classified Likely pathogenic in GLB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-10). Associated with GM1 gangliosidosis type 1.

What condition is associated with GLB1 p.Val164fs (c.488dup)?

GLB1 p.Val164fs (c.488dup) is associated with GM1 gangliosidosis type 1, GM1 gangliosidosis type 2, GM1 gangliosidosis type 3 (ClinVar).

How is GM1 gangliosidosis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

GLB1 p.Val164fs

c.488dup · VCV3589135

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

GM1 gangliosidosis type 1

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 5 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.67	GERP -3.6, phastCons 0.016

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

Variant & gene context

Gene: GLB1
Protein: p.Val164fs
Coding: c.488dup
MANE Select: NM_000404
Type: Duplication
Location: chr3:33065526 (GRCh38)
Gene constraint: LOEUF 0.938 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.19 · 8 PDB
Residue 164: an α-helix

Full GLB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

GM1 gangliosidosis type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: GM1 gangliosidosis type 2 GM1 gangliosidosis type 3 mucopolysaccharidosis type 4B

For GM1 gangliosidosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

GLB1 p.Val164= Likely benign ★ same residue
GLB1 c.75+2dup Pathogenic ★★ same condition
GLB1 p.Ala232fs Pathogenic/Likely pathogenic ★★ same condition
GLB1 p.Ala446fs Pathogenic/Likely pathogenic ★★ same condition
GLB1 p.Asn545fs Pathogenic ★★ same condition
GLB1 p.Asn669fs Pathogenic/Likely pathogenic ★★ same condition
GLB1 p.Asp198Ter Pathogenic ★★ same condition
GLB1 p.His534fs Pathogenic ★★ 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/glb1-p-val164fs (accessed [today's date]).

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