Is IDUA p.Pro496= (c.1488C>T) pathogenic?

IDUA p.Pro496= (c.1488C>T) is classified Likely benign in IDUA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-28). Very rare (popmax 0.00125%, sas); Associated with mucopolysaccharidosis type 1.

What condition is associated with IDUA p.Pro496= (c.1488C>T)?

IDUA p.Pro496= (c.1488C>T) is associated with mucopolysaccharidosis type 1 (ClinVar).

How common is IDUA p.Pro496= (c.1488C>T) in the general population?

IDUA p.Pro496= (c.1488C>T) is very rare (popmax 0.00125%, sas) (gnomAD).

How is Mucopolysaccharidosis type 1 inherited?

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

IDUA p.Pro496=

c.1488C>T · rs780479570 · VCV1560242

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00125%, sas)

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 -3.7	GERP -2.6
Overall
CADD	5.522	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00125% South Asian · 1/79,702 alleles

Overall 6.64e-05% 1/1,505,928 alleles · very rare exomes 1/1,353,912 · genomes 0/152,016 · 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.Pro496=
Coding: c.1488C>T
MANE Select: NM_000203
dbSNP: rs780479570
Type: single nucleotide variant
Location: chr4:1003121 (GRCh38)
Gene constraint: LOEUF 1.344 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.12 · 11 PDB
Residue 496: a UniProt-annotated variant site (in mps1h/s)

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.Pro496Arg Likely pathogenic ★★★ same residue
IDUA p.Pro496Leu Likely pathogenic ★★★ same residue
IDUA p.Pro496Ser Uncertain significance ★ ⚠ same residue
SLC26A1 p.Leu496Arg 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

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-pro496 (accessed [today's date]).

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