Is IDUA p.Arg45Pro (c.134G>C) pathogenic?

IDUA p.Arg45Pro (c.134G>C) is classified Uncertain significance in IDUA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-17). AlphaMissense: likely benign (0.0513); Very rare (popmax 0.00214%, amr); Associated with mucopolysaccharidosis type 1.

What condition is associated with IDUA p.Arg45Pro (c.134G>C)?

IDUA p.Arg45Pro (c.134G>C) is associated with mucopolysaccharidosis type 1 (ClinVar).

How common is IDUA p.Arg45Pro (c.134G>C) in the general population?

IDUA p.Arg45Pro (c.134G>C) is very rare (popmax 0.00214%, amr) (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.Arg45Pro (c.134G>C)?

AlphaMissense predicts likely benign (score 0.0513) — an in-silico prediction, not a clinical call.

IDUA p.Arg45Pro

c.134G>C · rs1448806369 · VCV1412970

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0513 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00214%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

mucopolysaccharidosis type 1

Computational evidence

Protein change
AlphaMissense	0.0513	likely benign
REVEL	0.473	indeterminate
SaProt	LLR -3.35	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.93	GERP -1.8, phastCons 0.001
Regional constraint	o/e 1.12	unconstrained · MANE · 17 kb · p 0.00042 · regional, not allelic
Overall
CADD	15.01	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00214% Admixed American · 1/46,780 alleles

Overall 0.000134% 2/1,493,382 alleles · very rare exomes 2/1,341,118 · genomes 0/152,264 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00214%	46,780
African / African-American	0.00146%	68,676

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.Arg45Pro
Coding: c.134G>C
MANE Select: NM_000203
dbSNP: rs1448806369
Type: single nucleotide variant
Location: chr4:987218 (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

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.Arg45= Likely benign ★ same residue
IDUA p.Arg45fs Pathogenic ★ same residue
IDUA p.Arg45Cys Uncertain significance ★★ ⚠ 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-arg45pro (accessed [today's date]).

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