Is GLB1 p.Val104= (c.312G>A) pathogenic?

GLB1 p.Val104= (c.312G>A) is classified Likely benign in GLB1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-03). Ultra-rare (popmax 0.012%, afr); Associated with mucopolysaccharidosis type 4B.

What condition is associated with GLB1 p.Val104= (c.312G>A)?

GLB1 p.Val104= (c.312G>A) is associated with mucopolysaccharidosis type 4B, GM1 gangliosidosis (ClinVar).

How common is GLB1 p.Val104= (c.312G>A) in the general population?

GLB1 p.Val104= (c.312G>A) is ultra-rare (popmax 0.012%, afr) (gnomAD).

How is Mucopolysaccharidosis type 4 inherited?

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

GLB1 p.Val104=

c.312G>A · rs113901133 · VCV1659283

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, 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 2.7	GERP -0.28, phastCons 1
Overall
CADD	10.92	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.012% African / African-American · 9/74,900 alleles

Filtering AF 0.00624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00149% 24/1,614,042 alleles · ultra-rare exomes 23/1,461,888 · genomes 1/152,154 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0192%	5,207
African / African-Americangrpmax	0.012%	8,322
East Asian	0.00223%	44,898
South Asian	0.0011%	91,074
European (non-Finnish)	8.47e-05%	1,180,036

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val104=
Coding: c.312G>A
MANE Select: NM_000404
dbSNP: rs113901133
Type: single nucleotide variant
Location: chr3:33068904 (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 104: an α-helix

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 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-val104 (accessed [today's date]).

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