Is IDUA p.Pro533= (c.1599G>A) pathogenic?

IDUA p.Pro533= (c.1599G>A) is classified Likely benign in IDUA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-18). Ultra-rare (popmax 0.02%, eas); Associated with mucopolysaccharidosis type 1.

What condition is associated with IDUA p.Pro533= (c.1599G>A)?

IDUA p.Pro533= (c.1599G>A) is associated with mucopolysaccharidosis type 1 (ClinVar).

How common is IDUA p.Pro533= (c.1599G>A) in the general population?

IDUA p.Pro533= (c.1599G>A) is ultra-rare (popmax 0.02%, eas) (gnomAD).

How is Mucopolysaccharidosis type 1 inherited?

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

IDUA p.Pro533=

c.1599G>A · rs773947412 · VCV1154981

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, eas)

Conditions

mucopolysaccharidosis type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.6	GERP -3.1
Overall
CADD	5.839	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% East Asian · 8/40,034 alleles

Filtering AF 0.00986% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00717%

Overall 0.00222% 34/1,528,132 alleles · ultra-rare exomes 27/1,376,056 · genomes 7/152,076 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.02%	5,004
African / African-American	0.00417%	23,974
Remaining individualsnot grpmax-eligible	0.00336%	29,755
Admixed American	0.00198%	50,522
European (non-Finnish)	0.00175%	57,217

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.Pro533=
Coding: c.1599G>A
MANE Select: NM_000203
dbSNP: rs773947412
Type: single nucleotide variant
Location: chr4:1003419 (GRCh38)
Gene constraint: LOEUF 1.344 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.12 · 11 PDB
Residue 533: a β-strand; a UniProt-annotated variant site (in mps1h and mps1h/s; in 3% of the mps1h patients; reduces catalytic activity and protein stability)

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.Pro533Arg Pathogenic ★★★ same residue
IDUA p.Pro533Leu Pathogenic/Likely pathogenic ★★ same residue
IDUA p.Pro533Thr Likely pathogenic ★ ⚠ same residue
IDUA p.Pro533Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
IDUA p.Pro533Ser Conflicting classifications of pathogenicity ★ ⚠ 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

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-pro533 (accessed [today's date]).

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