Is GLB1 p.Pro2= (c.6G>A) pathogenic?

GLB1 p.Pro2= (c.6G>A) is classified Likely benign in GLB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-08). Absent from gnomAD v4.1; Associated with mucopolysaccharidosis type 4B.

What condition is associated with GLB1 p.Pro2= (c.6G>A)?

GLB1 p.Pro2= (c.6G>A) is associated with mucopolysaccharidosis type 4B, GM1 gangliosidosis (ClinVar).

How common is GLB1 p.Pro2= (c.6G>A) in the general population?

GLB1 p.Pro2= (c.6G>A) is absent from gnomAD v4.1 (gnomAD).

How is Mucopolysaccharidosis type 4 inherited?

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

GLB1 p.Pro2=

c.6G>A · rs1160901537 · VCV2932642

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,512)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -3.6
Overall
CADD	9.009	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,612,512). 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.Pro2=
Coding: c.6G>A
MANE Select: NM_000404
dbSNP: rs1160901537
Type: single nucleotide variant
Location: chr3:33097080 (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

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.Pro2Thr Uncertain significance ★★ ⚠ same residue
GLB1 p.Pro2Ala Uncertain significance ★ ⚠ same residue
GLB1 p.Pro2Leu Uncertain significance ★ ⚠ same residue
GLB1 c.1144-2A>G Pathogenic/Likely pathogenic ★★ same condition
GLB1 c.1233+1G>A Pathogenic/Likely pathogenic ★★ same condition
GLB1 c.1347+1G>T Likely pathogenic ★★ same condition
GLB1 c.1479+1G>A Pathogenic ★★ same condition
GLB1 c.1480-2A>G 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-pro2 (accessed [today's date]).

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