Is GLB1 p.Ile55fs (c.163del) pathogenic?

GLB1 p.Ile55fs (c.163del) is classified Pathogenic in GLB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-15). Very rare (popmax 0.000254%, nfe); Associated with GM1 gangliosidosis.

What condition is associated with GLB1 p.Ile55fs (c.163del)?

GLB1 p.Ile55fs (c.163del) is associated with GM1 gangliosidosis, mucopolysaccharidosis type 4B (ClinVar).

How common is GLB1 p.Ile55fs (c.163del) in the general population?

GLB1 p.Ile55fs (c.163del) is very rare (popmax 0.000254%, nfe) (gnomAD).

How is GM1 gangliosidosis inherited?

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

GLB1 p.Ile55fs

c.163del · rs1575475703 · VCV657106

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

GM1 gangliosidosis

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 2 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,038 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,842 alleles · very rare

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: GLB1
Protein: p.Ile55fs
Coding: c.163del
MANE Select: NM_000404
dbSNP: rs1575475703
Type: Deletion
Location: chr3:33072626 (GRCh38)
Gene constraint: LOEUF 0.938 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.19 · 8 PDB

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

Disease context

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

Also linked: mucopolysaccharidosis type 4B

For GM1 gangliosidosis (Orphanet):

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

Similar variants

GLB1 p.Ile55= Likely benign ★ same residue
GLB1 c.65_75+1del Pathogenic/Likely pathogenic ★★ same condition
GLB1 c.769_792+13del Pathogenic/Likely pathogenic ★★ same condition
GLB1 p.Asn490del Likely pathogenic ★★ same condition
GLB1 p.Gln234fs Pathogenic/Likely pathogenic ★★ same condition
GLB1 p.Gly178fs Pathogenic/Likely pathogenic ★★ same condition
GLB1 p.Gly278fs Pathogenic ★★ same condition
GLB1 p.Gly467fs Pathogenic/Likely 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-ile55fs (accessed [today's date]).

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