Is IDUA p.Pro3fs (c.-4_6dup) pathogenic?

IDUA p.Pro3fs (c.-46dup) is classified Likely pathogenic in IDUA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-17). Associated with Scheie syndrome.

What condition is associated with IDUA p.Pro3fs (c.-4_6dup)?

IDUA p.Pro3fs (c.-4_6dup) is associated with Scheie syndrome, Hurler syndrome, Hurler-Scheie syndrome (ClinVar).

How is Mucopolysaccharidosis type 1 inherited?

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

IDUA p.Pro3fs

c.-4_6dup · VCV3591448

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Scheie syndrome

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 1 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.4	GERP -1.7

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

Variant & gene context

Gene: IDUA
Protein: p.Pro3fs
Coding: c.-4_6dup
MANE Select: NM_000203
Type: Duplication
Location: chr4:987076 (GRCh38)
Gene constraint: LOEUF 1.344 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.12 · 11 PDB

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

Disease context

Scheie syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Hurler syndrome Hurler-Scheie syndrome

For Mucopolysaccharidosis type 1 (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

IDUA p.Glu207fs Pathogenic ★★★ same condition
IDUA p.Tyr296_Asp298dup Likely pathogenic ★★★ same condition
IDUA p.Asn181fs Pathogenic/Likely pathogenic ★★ same condition
IDUA p.Gly466fs Pathogenic/Likely pathogenic ★★ same condition
IDUA p.Thr293_Tyr296dup Pathogenic/Likely pathogenic ★★ same condition
IDUA p.Tyr475fs Pathogenic ★★ same condition
IDUA p.Val606fs Pathogenic/Likely pathogenic ★★ same condition
IDUA p.Pro214dup Uncertain significance ★★ 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/idua-p-pro3fs (accessed [today's date]).

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