Is GLB1 p.Phe357fs (c.1071_1073delinsGG) pathogenic?

GLB1 p.Phe357fs (c.10711073delinsGG) is classified Pathogenic/Likely pathogenic in GLB1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-14). Absent from gnomAD; Associated with GM1 gangliosidosis type 1.

What condition is associated with GLB1 p.Phe357fs (c.1071_1073delinsGG)?

GLB1 p.Phe357fs (c.1071_1073delinsGG) is associated with GM1 gangliosidosis type 1, mucopolysaccharidosis type 4B (ClinVar).

How common is GLB1 p.Phe357fs (c.1071_1073delinsGG) in the general population?

GLB1 p.Phe357fs (c.1071_1073delinsGG) is absent from gnomAD (gnomAD).

How is GM1 gangliosidosis inherited?

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

GLB1 p.Phe357fs

c.1071_1073delinsGG · rs2471279230 · VCV2585128

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 11 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.73	GERP -2, phastCons 0.26

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: GLB1
Protein: p.Phe357fs
Coding: c.1071_1073delinsGG
MANE Select: NM_000404
dbSNP: rs2471279230
Type: Indel
Location: chr3:33024321 (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 type 1 — 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.Phe357Leu Uncertain significance ★★ ⚠ same residue
GLB1 p.Trp273Leu Pathogenic/Likely pathogenic ★★ same condition
GLB1 p.Leu12fs Likely pathogenic ★ same condition
GLB1 p.Leu146fs Likely pathogenic ★ same condition
GLB1 p.Pro397Ser Likely pathogenic ★ same condition
GLB1 p.Thr466fs Likely pathogenic ★ same condition
GLB1 c.914+15_914+16delinsAGTGTGAACTTGTGAGTGTTT Uncertain significance ★ same condition
GLB1 p.Gln46Pro 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/glb1-p-phe357fs (accessed [today's date]).

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