Is GUSB p.Ile170fs (c.507dup) pathogenic?

GUSB p.Ile170fs (c.507dup) is classified Pathogenic in GUSB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-20). Absent from gnomAD; Associated with mucopolysaccharidosis type 7.

What condition is associated with GUSB p.Ile170fs (c.507dup)?

GUSB p.Ile170fs (c.507dup) is associated with mucopolysaccharidosis type 7 (ClinVar).

How common is GUSB p.Ile170fs (c.507dup) in the general population?

GUSB p.Ile170fs (c.507dup) is absent from gnomAD (gnomAD).

How is Mucopolysaccharidosis type 7 inherited?

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

GUSB p.Ile170fs

c.507dup · rs2484841000 · VCV2863642

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	predicted	premature termination codon in exon 3 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.58	GERP 0.31
Region caveats
Repeat context	tandem	(TGGTGA)n simple repeat · ambiguous alignment · confidence, not pathogenicity

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GUSB
Protein: p.Ile170fs
Coding: c.507dup
MANE Select: NM_000181
dbSNP: rs2484841000
Type: Duplication
Location: chr7:65979800 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.35 · 2 PDB
Residue 170: 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.Ile170= Likely benign ★ same residue
GUSB p.Asn486Ter Pathogenic ★★ same condition
GUSB c.1790-2dup Uncertain significance ★★ same condition
GUSB p.Arg600fs Pathogenic ★ 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

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-ile170fs (accessed [today's date]).

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