Is GLB1 p.Pro367Ser (c.1099C>T) pathogenic?

GLB1 p.Pro367Ser (c.1099C>T) is classified Uncertain significance in GLB1 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely benign (0.1057); Very rare (popmax 0.00113%, sas); Associated with GM1 gangliosidosis type 1.

What condition is associated with GLB1 p.Pro367Ser (c.1099C>T)?

GLB1 p.Pro367Ser (c.1099C>T) is associated with GM1 gangliosidosis type 1 (ClinVar).

How common is GLB1 p.Pro367Ser (c.1099C>T) in the general population?

GLB1 p.Pro367Ser (c.1099C>T) is very rare (popmax 0.00113%, sas) (gnomAD).

How is GM1 gangliosidosis inherited?

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

What do computational predictors say about GLB1 p.Pro367Ser (c.1099C>T)?

AlphaMissense predicts likely benign (score 0.1057) — an in-silico prediction, not a clinical call.

GLB1 p.Pro367Ser

c.1099C>T · rs1697636883 · VCV1332870

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1057 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00113%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

GM1 gangliosidosis type 1

Computational evidence

Protein change
AlphaMissense	0.1057	likely benign
REVEL	0.646	pathogenic-leaning
SaProt	LLR -8.70	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 100 kb · p 0.044 · regional, not allelic
Overall
CADD	26.5	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 0.00113% South Asian · 1/88,806 alleles

Overall 6.37e-05% 1/1,570,420 alleles · very rare exomes 1/1,455,894 · genomes 0/114,526 · 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.Pro367Ser
Coding: c.1099C>T
MANE Select: NM_000404
dbSNP: rs1697636883
Type: single nucleotide variant
Location: chr3:33024295 (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 367: an α-helix

Full GLB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

GM1 gangliosidosis type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For GM1 gangliosidosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

GLB1 p.Pro367= Likely benign ★★ same residue
GLB1 p.Pro367Leu 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
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-pro367ser (accessed [today's date]).

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