Is GUSB p.Arg600fs (c.1798dup) pathogenic?

GUSB p.Arg600fs (c.1798dup) is classified Pathogenic in GUSB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-09). Very rare (popmax 8.48e-05%, nfe); Associated with mucopolysaccharidosis type 7.

What condition is associated with GUSB p.Arg600fs (c.1798dup)?

GUSB p.Arg600fs (c.1798dup) is associated with mucopolysaccharidosis type 7 (ClinVar).

How common is GUSB p.Arg600fs (c.1798dup) in the general population?

GUSB p.Arg600fs (c.1798dup) 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.Arg600fs

c.1798dup · rs1554303791 · VCV2962907

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

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.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (12 of 12) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,532 alleles

Overall 6.84e-05% 1/1,461,570 alleles · very rare

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.Arg600fs
Coding: c.1798dup
MANE Select: NM_000181
dbSNP: rs1554303791
Type: Duplication
Location: chr7:65961054 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.35 · 2 PDB
Residue 600: a β-strand

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 p.Asn486Ter Pathogenic ★★ same condition
GUSB p.Ile170fs Pathogenic ★★ same condition
GUSB c.1790-2dup Uncertain significance ★★ same condition
GUSB p.Asn604fs Pathogenic ★ same condition
GUSB p.Asp230Ter Pathogenic ★ same condition
GUSB p.Gly26fs Pathogenic ★ same condition
GUSB p.His509fs Likely pathogenic ★ same condition
GUSB p.Ile586fs 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-arg600fs (accessed [today's date]).

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