Is IDUA p.Pro294= (c.882C>T) pathogenic?

IDUA p.Pro294= (c.882C>T) is classified Likely benign in IDUA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-11). Ultra-rare (popmax 0.016%, afr); Associated with Inborn genetic diseases.

What condition is associated with IDUA p.Pro294= (c.882C>T)?

IDUA p.Pro294= (c.882C>T) is associated with Inborn genetic diseases, mucopolysaccharidosis type 1 (ClinVar).

How common is IDUA p.Pro294= (c.882C>T) in the general population?

IDUA p.Pro294= (c.882C>T) is ultra-rare (popmax 0.016%, afr) (gnomAD).

IDUA p.Pro294=

c.882C>T · rs762825338 · VCV1141288

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.177	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.069	GERP -2.9
Overall
CADD	8.565	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.016% African / African-American · 12/74,798 alleles

Filtering AF 0.00923% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00723%

Overall 0.000754% 12/1,591,948 alleles · ultra-rare

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.Pro294=
Coding: c.882C>T
MANE Select: NM_000203
dbSNP: rs762825338
Type: single nucleotide variant
Location: chr4:1002071 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mucopolysaccharidosis type 1

Similar variants

SLC26A1 p.Thr294Met Uncertain significance ★★ ⚠ same residue
IDUA p.Pro294Thr 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
IDUA c.1403-1G>T 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-pro294 (accessed [today's date]).

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