Is GLB1 p.Arg109= (c.327G>T) pathogenic?

GLB1 p.Arg109= (c.327G>T) is classified Likely benign in GLB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-13). Very rare (popmax 0.00267%, afr); Associated with mucopolysaccharidosis type 4B.

What condition is associated with GLB1 p.Arg109= (c.327G>T)?

GLB1 p.Arg109= (c.327G>T) is associated with mucopolysaccharidosis type 4B, GM1 gangliosidosis (ClinVar).

How common is GLB1 p.Arg109= (c.327G>T) in the general population?

GLB1 p.Arg109= (c.327G>T) is very rare (popmax 0.00267%, afr) (gnomAD).

How is Mucopolysaccharidosis type 4 inherited?

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

GLB1 p.Arg109=

c.327G>T · rs751602590 · VCV1081707

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

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 0.85	GERP -0.28, phastCons 0.28
Overall
CADD	8.184	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,886 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,613,986 alleles · very rare exomes 0/1,461,894 · genomes 3/152,092 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,443
Admixed American	0.00167%	59,974

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.Arg109=
Coding: c.327G>T
MANE Select: NM_000404
dbSNP: rs751602590
Type: single nucleotide variant
Location: chr3:33068889 (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 109: an α-helix; a UniProt-annotated variant site (in)

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.Arg109Trp Benign/Likely benign ★★ same residue
GLB1 p.Arg109Gln Uncertain significance ★ ⚠ same residue
GLB1 p.Arg109Pro Conflicting classifications of pathogenicity ★ ⚠ 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-arg109 (accessed [today's date]).

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