Is GLB1 p.Arg68= (c.204G>T) pathogenic?

GLB1 p.Arg68= (c.204G>T) is classified Likely benign in GLB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-19). Very rare (popmax 8.47e-05%, nfe); Associated with mucopolysaccharidosis type 4B.

What condition is associated with GLB1 p.Arg68= (c.204G>T)?

GLB1 p.Arg68= (c.204G>T) is associated with mucopolysaccharidosis type 4B, GM1 gangliosidosis (ClinVar).

How common is GLB1 p.Arg68= (c.204G>T) in the general population?

GLB1 p.Arg68= (c.204G>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Mucopolysaccharidosis type 4 inherited?

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

GLB1 p.Arg68=

c.204G>T · rs1309516618 · VCV755403

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

mucopolysaccharidosis type 4B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.76	GERP -0.33, phastCons 1
Overall
CADD	12.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,050 alleles

Overall 6.2e-05% 1/1,613,986 alleles · very rare exomes 1/1,461,640 · genomes 0/152,346 · joint denominator

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.Arg68=
Coding: c.204G>T
MANE Select: NM_000404
dbSNP: rs1309516618
Type: single nucleotide variant
Location: chr3:33072585 (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 68: an α-helix; a UniProt-annotated variant site (in gm1g2; 7.4% of wild-type galactosidase activity); a UniProt-annotated variant site (in gm1g2 and gm1g1; loss of 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.Arg68Gln Pathogenic/Likely pathogenic ★★ ⚠ same residue
GLB1 p.Arg68Trp Pathogenic ★★ same residue
GLB1 p.Arg68Gly Likely pathogenic ★ same residue
GLB1 p.Arg68Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
GLB1 p.Arg68Pro Likely pathogenic ★ same residue
TMPPE p.Val68Gly Uncertain significance ★ ⚠ same residue
GLB1 c.1144-2A>G Pathogenic/Likely pathogenic ★★ same condition
GLB1 c.1233+1G>A 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-arg68 (accessed [today's date]).

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