Is GLB1 p.Pro429Ser (c.1285C>T) pathogenic?

GLB1 p.Pro429Ser (c.1285C>T) is classified Conflicting classifications of pathogenicity in GLB1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.0978); Rare (popmax 0.378%, afr); Associated with mucopolysaccharidosis type 4B.

What condition is associated with GLB1 p.Pro429Ser (c.1285C>T)?

GLB1 p.Pro429Ser (c.1285C>T) is associated with mucopolysaccharidosis type 4B, GM1 gangliosidosis type 1, GM1 gangliosidosis type 2 (ClinVar).

How common is GLB1 p.Pro429Ser (c.1285C>T) in the general population?

GLB1 p.Pro429Ser (c.1285C>T) is rare (popmax 0.378%, afr) (gnomAD).

How is Mucopolysaccharidosis type 4 inherited?

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

What do computational predictors say about GLB1 p.Pro429Ser (c.1285C>T)?

AlphaMissense predicts likely benign (score 0.0978) — an in-silico prediction, not a clinical call.

GLB1 p.Pro429Ser

c.1285C>T · rs180869784 · VCV242561

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0978 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.378%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mucopolysaccharidosis type 4B

Computational evidence

Protein change
AlphaMissense	0.0978	likely benign
REVEL	0.285	benign-leaning
SaProt	LLR -8.72	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -3.5, phastCons 0.95
Regional constraint	o/e 0.93	unconstrained · MANE · 100 kb · p 0.044 · regional, not allelic
Overall
CADD	8.697	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.378% African / African-American · 283/74,950 alleles

Filtering AF 0.341% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.327%

Overall 0.0191% 309/1,613,978 alleles · rare exomes 153/1,461,876 · genomes 156/152,102 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.378%	265
Admixed American	0.025%	3,999
Remaining individualsnot grpmax-eligible	0.008%	12,502
European (non-Finnish)	0.000508%	196,669

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.Pro429Ser
Coding: c.1285C>T
MANE Select: NM_000404
dbSNP: rs180869784
Type: single nucleotide variant
Location: chr3:33018510 (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 429: a β-strand

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 type 1 GM1 gangliosidosis type 2 GM1 gangliosidosis type 3 GM1 gangliosidosis

For Mucopolysaccharidosis type 4 (Orphanet):

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

Similar variants

GLB1 p.Pro429Leu 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.1480-1G>C Pathogenic/Likely pathogenic ★★ same condition
GLB1 c.1480-2A>G Pathogenic ★★ same condition
GLB1 c.245+1G>A 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-pro429ser (accessed [today's date]).

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