Is IDUA p.Pro55fs (c.164del) pathogenic?

IDUA p.Pro55fs (c.164del) is classified Pathogenic in IDUA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-30). Very rare (popmax 8.48e-05%, nfe); Associated with Hurler syndrome.

What condition is associated with IDUA p.Pro55fs (c.164del)?

IDUA p.Pro55fs (c.164del) is associated with Hurler syndrome (ClinVar).

How common is IDUA p.Pro55fs (c.164del) in the general population?

IDUA p.Pro55fs (c.164del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Mucopolysaccharidosis type 1 inherited?

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

IDUA p.Pro55fs

c.164del · rs727503966 · VCV167189

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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

Conditions

Hurler 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 2 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1, 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) · 1/1,179,824 alleles

Overall 6.2e-05% 1/1,612,180 alleles · very rare exomes 1/1,459,878 · genomes 0/152,302 · 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: IDUA
Protein: p.Pro55fs
Coding: c.164del
MANE Select: NM_000203
dbSNP: rs727503966
Type: Deletion
Location: chr4:987809 (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

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

For Mucopolysaccharidosis type 1 (Orphanet):

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

Similar variants

IDUA p.Arg531fs Pathogenic ★★★ same condition
IDUA p.Asp292fs Pathogenic ★★★ same condition
IDUA p.Asp349del Pathogenic ★★★ same condition
IDUA p.His358_Thr364del Likely pathogenic ★★★ same condition
IDUA p.His539fs Pathogenic ★★★ same condition
IDUA p.Ser16_Ala19del Pathogenic ★★★ same condition
IDUA p.Thr388fs Pathogenic ★★★ same condition
IDUA p.Thr417_His425del 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/idua-p-pro55fs (accessed [today's date]).

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