Is GLB1 p.Pro397Ser (c.1188_1189delinsCT) pathogenic?

GLB1 p.Pro397Ser (c.11881189delinsCT) is classified Likely pathogenic in GLB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-24). Absent from gnomAD; Associated with mucopolysaccharidosis type 4B.

What condition is associated with GLB1 p.Pro397Ser (c.1188_1189delinsCT)?

GLB1 p.Pro397Ser (c.1188_1189delinsCT) is associated with mucopolysaccharidosis type 4B, GM1 gangliosidosis (ClinVar).

How common is GLB1 p.Pro397Ser (c.1188_1189delinsCT) in the general population?

GLB1 p.Pro397Ser (c.1188_1189delinsCT) is absent from gnomAD (gnomAD).

How is Mucopolysaccharidosis type 4 inherited?

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

GLB1 p.Pro397Ser

c.1188_1189delinsCT · rs2471270873 · VCV2941816

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

mucopolysaccharidosis type 4B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.7	GERP 0.62, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 100 kb · p 0.044 · regional, not allelic

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.Pro397Ser
Coding: c.1188_1189delinsCT
MANE Select: NM_000404
dbSNP: rs2471270873
Type: Indel
Location: chr3:33021610 (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 397: a UniProt-annotated variant site (in mps4b; 24.0% of wild-type galactosidase activity)

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

Disease context

mucopolysaccharidosis type 4B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: GM1 gangliosidosis

For Mucopolysaccharidosis type 4 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy
Prevalence: <1 / 1 000 000 (Sweden)

Similar variants

GLB1 p.Phe357fs Pathogenic/Likely pathogenic ★★ same condition
GLB1 p.Trp273Leu Pathogenic/Likely pathogenic ★★ same condition
GLB1 p.Leu12fs Likely pathogenic ★ same condition
GLB1 p.Leu146fs 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
GLB1 p.Gly575Val 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-pro397ser (accessed [today's date]).

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