Is IDUA p.Pro650= (c.1950G>C) pathogenic?

IDUA p.Pro650= (c.1950G>C) is classified Likely benign in IDUA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-03). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with IDUA p.Pro650= (c.1950G>C)?

IDUA p.Pro650= (c.1950G>C) is associated with Inborn genetic diseases, mucopolysaccharidosis type 1 (ClinVar).

How common is IDUA p.Pro650= (c.1950G>C) in the general population?

IDUA p.Pro650= (c.1950G>C) is absent from gnomAD v4.1 (gnomAD).

IDUA p.Pro650=

c.1950G>C · rs112884255 · VCV2108021

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

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 -2.1	GERP -2.6
Overall
CADD	1.102	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: IDUA
Protein: p.Pro650=
Coding: c.1950G>C
MANE Select: NM_000203
dbSNP: rs112884255
Type: single nucleotide variant
Location: chr4:1004381 (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

IDUA p.Pro650Leu Uncertain significance ★ ⚠ same residue
IDUA p.Pro650fs 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
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-pro650 (accessed [today's date]).

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