Is GUSB p.Asp264= (c.792T>C) pathogenic?

GUSB p.Asp264= (c.792T>C) is classified Likely benign in GUSB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-30). Very rare (popmax 8.48e-05%, nfe); Associated with mucopolysaccharidosis type 7.

What condition is associated with GUSB p.Asp264= (c.792T>C)?

GUSB p.Asp264= (c.792T>C) is associated with mucopolysaccharidosis type 7 (ClinVar).

How common is GUSB p.Asp264= (c.792T>C) in the general population?

GUSB p.Asp264= (c.792T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Mucopolysaccharidosis type 7 inherited?

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

GUSB p.Asp264=

c.792T>C · rs1791558497 · VCV2963670

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

mucopolysaccharidosis type 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.57	GERP 0.57, phastCons 0.002
Overall
CADD	2.117	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,728 alleles

Overall 6.2e-05% 1/1,613,674 alleles · very rare exomes 1/1,461,424 · genomes 0/152,250 · 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: GUSB
Protein: p.Asp264=
Coding: c.792T>C
MANE Select: NM_000181
dbSNP: rs1791558497
Type: single nucleotide variant
Location: chr7:65976135 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.35 · 2 PDB

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

Disease context

mucopolysaccharidosis type 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Mucopolysaccharidosis type 7 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Antenatal, Childhood, Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

GUSB c.1244+1G>A Pathogenic ★★ same condition
GUSB c.581+1G>A Pathogenic/Likely pathogenic ★★ same condition
GUSB c.724+1G>T Pathogenic/Likely pathogenic ★★ same condition
GUSB p.Ala619Val Pathogenic/Likely pathogenic ★★ same condition
GUSB p.Arg110Ter Pathogenic/Likely pathogenic ★★ same condition
GUSB p.Arg167Ter Pathogenic/Likely pathogenic ★★ same condition
GUSB p.Arg216Trp Pathogenic/Likely pathogenic ★★ same condition
GUSB p.Arg357Ter 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/gusb-p-asp264 (accessed [today's date]).

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