Is GLB1 p.Ser150= (c.450C>T) pathogenic?

GLB1 p.Ser150= (c.450C>T) is classified Likely benign in GLB1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-26). Ultra-rare (popmax 0.0333%, afr); Associated with GM1 gangliosidosis.

What condition is associated with GLB1 p.Ser150= (c.450C>T)?

GLB1 p.Ser150= (c.450C>T) is associated with GM1 gangliosidosis, mucopolysaccharidosis type 4B (ClinVar).

How common is GLB1 p.Ser150= (c.450C>T) in the general population?

GLB1 p.Ser150= (c.450C>T) is ultra-rare (popmax 0.0333%, afr) (gnomAD).

How is GM1 gangliosidosis inherited?

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

GLB1 p.Ser150=

c.450C>T · rs140353187 · VCV1136346

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0333%, afr)

Conditions

GM1 gangliosidosis

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 -2.7	GERP -3.6
Overall
CADD	1.066	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0333% African / African-American · 25/75,046 alleles

Filtering AF 0.0231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00428% 69/1,614,022 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0333%	3,002
Middle Eastern	0.0165%	6,060
Admixed American	0.01%	10,001
Finnishnot grpmax-eligible	0.00781%	12,801
Remaining individualsnot grpmax-eligible	0.0064%	15,623
East Asian	0.00223%	44,880
South Asian	0.0022%	45,534
European (non-Finnish)	0.00212%	47,198

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.Ser150=
Coding: c.450C>T
MANE Select: NM_000404
dbSNP: rs140353187
Type: single nucleotide variant
Location: chr3:33068237 (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 — 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 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
GLB1 c.245+1G>A Pathogenic ★★ same condition
GLB1 c.396+2T>C Pathogenic/Likely pathogenic ★★ same condition
GLB1 c.397-1G>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-ser150 (accessed [today's date]).

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