Is IDUA p.Arg89Pro (c.266G>C) pathogenic?

IDUA p.Arg89Pro (c.266G>C) is classified Likely pathogenic in IDUA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-23). AlphaMissense: likely pathogenic (0.9719); Absent from gnomAD v4.1; Associated with mucopolysaccharidosis type 1.

What condition is associated with IDUA p.Arg89Pro (c.266G>C)?

IDUA p.Arg89Pro (c.266G>C) is associated with mucopolysaccharidosis type 1 (ClinVar).

How common is IDUA p.Arg89Pro (c.266G>C) in the general population?

IDUA p.Arg89Pro (c.266G>C) is absent from gnomAD v4.1 (gnomAD).

How is Mucopolysaccharidosis type 1 inherited?

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

What do computational predictors say about IDUA p.Arg89Pro (c.266G>C)?

AlphaMissense predicts likely pathogenic (score 0.9719) — an in-silico prediction, not a clinical call.

IDUA p.Arg89Pro

c.266G>C · VCV4697985

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9719 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mucopolysaccharidosis type 1

Computational evidence

Protein change
AlphaMissense	0.9719	likely pathogenic ✓ concordant with ClinVar · top 3% in IDUA
REVEL	0.944	strongly pathogenic-leaning
SaProt	LLR -14.26	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.49	donor loss, 5 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 12	GERP 0.64, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 17 kb · p 0.00042 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: IDUA
Protein: p.Arg89Pro
Coding: c.266G>C
MANE Select: NM_000203
Type: single nucleotide variant
Location: chr4:987916 (GRCh38)
Gene constraint: LOEUF 1.344 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.12 · 11 PDB
Residue 89: a β-strand; a UniProt-annotated variant site (in mps1s)

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

Disease context

mucopolysaccharidosis type 1 — 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.Arg89Gln Pathogenic ★★★ same residue
IDUA p.Arg89Gly Pathogenic/Likely pathogenic ★★ same residue
IDUA p.Arg89= Likely benign ★ same residue
IDUA c.1190-10C>A Likely pathogenic ★★★ same condition
IDUA c.1190-1G>A Pathogenic ★★★ same condition
IDUA c.1402+1G>A Likely pathogenic ★★★ same condition
IDUA c.1402+1G>T Likely pathogenic ★★★ same condition
IDUA c.1402+2T>G 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-arg89pro (accessed [today's date]).

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