Is GLB1 p.Phe41= (c.123C>T) pathogenic?

GLB1 p.Phe41= (c.123C>T) is classified Likely benign in GLB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-22). Very rare (popmax 0.000508%, nfe); Associated with GM1 gangliosidosis.

What condition is associated with GLB1 p.Phe41= (c.123C>T)?

GLB1 p.Phe41= (c.123C>T) is associated with GM1 gangliosidosis, mucopolysaccharidosis type 4B (ClinVar).

How common is GLB1 p.Phe41= (c.123C>T) in the general population?

GLB1 p.Phe41= (c.123C>T) is very rare (popmax 0.000508%, nfe) (gnomAD).

How is GM1 gangliosidosis inherited?

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

GLB1 p.Phe41=

c.123C>T · rs1559411842 · VCV1160930

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Conditions

GM1 gangliosidosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.21	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 7.6	GERP 2.9, phastCons 1
Overall
CADD	15.24	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000508% European (non-Finnish) · 6/1,180,036 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,614,176 alleles · very rare exomes 6/1,461,864 · genomes 0/152,312 · 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.Phe41=
Coding: c.123C>T
MANE Select: NM_000404
dbSNP: rs1559411842
Type: single nucleotide variant
Location: chr3:33072666 (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 41: a β-strand

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

TMPPE p.Arg41Cys Uncertain significance ★ ⚠ same residue
TMPPE p.Arg41His 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-phe41 (accessed [today's date]).

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