Is GLB1 p.Phe415fs (c.1242del) pathogenic?

GLB1 p.Phe415fs (c.1242del) is classified Likely pathogenic in GLB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-12). Associated with GM1 gangliosidosis type 1.

What condition is associated with GLB1 p.Phe415fs (c.1242del)?

GLB1 p.Phe415fs (c.1242del) 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.Phe415fs

c.1242del · VCV3589132

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 13 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1

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

Variant & gene context

Gene: GLB1
Protein: p.Phe415fs
Coding: c.1242del
MANE Select: NM_000404
Type: Deletion
Location: chr3:33018553 (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 415: a β-strand

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 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
GLB1 p.Gly526fs 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-phe415fs (accessed [today's date]).

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