Is IDUA p.Pro183= (c.549A>G) pathogenic?

IDUA p.Pro183= (c.549A>G) is classified Likely benign in IDUA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). Very rare (popmax 8.47e-05%, nfe); Associated with mucopolysaccharidosis type 1.

What condition is associated with IDUA p.Pro183= (c.549A>G)?

IDUA p.Pro183= (c.549A>G) is associated with mucopolysaccharidosis type 1 (ClinVar).

How common is IDUA p.Pro183= (c.549A>G) in the general population?

IDUA p.Pro183= (c.549A>G) is very rare (popmax 8.47e-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.Pro183=

c.549A>G · rs2534083023 · VCV2115706

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

mucopolysaccharidosis type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.102	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.1	GERP -2.4
Overall
CADD	1.437	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,964 alleles

Overall 6.2e-05% 1/1,613,290 alleles · very rare exomes 1/1,460,990 · genomes 0/152,300 · 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.Pro183=
Coding: c.549A>G
MANE Select: NM_000203
dbSNP: rs2534083023
Type: single nucleotide variant
Location: chr4:1001523 (GRCh38)
Gene constraint: LOEUF 1.344 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.12 · 11 PDB
Residue 183: an α-helix

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.Pro183Ser Uncertain significance ★★★ ⚠ same residue
IDUA p.Pro183Arg Likely pathogenic ★ same residue
SLC26A1 p.Ala183Thr Uncertain significance ★★ ⚠ same residue
IDUA p.Pro183Ala 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-pro183 (accessed [today's date]).

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