Is IDUA p.Val80= (c.240C>G) pathogenic?

IDUA p.Val80= (c.240C>G) is classified Conflicting classifications of pathogenicity in IDUA (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-08-18). Ultra-rare (popmax 0.0307%, afr); Associated with mucopolysaccharidosis type 1.

What condition is associated with IDUA p.Val80= (c.240C>G)?

IDUA p.Val80= (c.240C>G) is associated with mucopolysaccharidosis type 1 (ClinVar).

How common is IDUA p.Val80= (c.240C>G) in the general population?

IDUA p.Val80= (c.240C>G) is ultra-rare (popmax 0.0307%, afr) (gnomAD).

How is Mucopolysaccharidosis type 1 inherited?

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

IDUA p.Val80=

c.240C>G · rs373277285 · VCV1149120

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0307%, afr)

Conditions

mucopolysaccharidosis type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.014	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.4	GERP -0.58
Overall
CADD	7.129	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0307% African / African-American · 23/74,992 alleles

Filtering AF 0.021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0178%

Overall 0.00143% 23/1,610,610 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.Val80=
Coding: c.240C>G
MANE Select: NM_000203
dbSNP: rs373277285
Type: single nucleotide variant
Location: chr4:987890 (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

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.Val80Ile Uncertain significance ★ ⚠ same residue
SLC26A1 p.Gly80= Likely benign ★ same residue
IDUA p.Val80Ala 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

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-val80 (accessed [today's date]).

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