Is IDS p.His179= (c.537T>C) pathogenic?

IDS p.His179= (c.537T>C) is classified Uncertain significance in IDS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-04-18). Very rare (popmax 0.00175%, sas); Associated with mucopolysaccharidosis type 3A.

What condition is associated with IDS p.His179= (c.537T>C)?

IDS p.His179= (c.537T>C) is associated with mucopolysaccharidosis type 3A (ClinVar).

How common is IDS p.His179= (c.537T>C) in the general population?

IDS p.His179= (c.537T>C) is very rare (popmax 0.00175%, sas) (gnomAD).

How is Mucopolysaccharidosis type 3 inherited?

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

IDS p.His179=

c.537T>C · VCV4069634

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00175%, sas)

Conditions

mucopolysaccharidosis type 3A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.28	GERP -0.95, phastCons 0.36
Overall
CADD	5.434	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00175% South Asian · 1/56,997 alleles

Overall 8.25e-05% 1/1,211,715 alleles · very rare exomes 1/1,097,573 · genomes 0/114,142 · 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: IDS
Protein: p.His179=
Coding: c.537T>C
MANE Select: NM_000202
Type: single nucleotide variant
Location: chrX:149498278 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB

Full IDS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mucopolysaccharidosis type 3A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Mucopolysaccharidosis type 3 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Brazil)

Similar variants

IDS p.His179Arg Uncertain significance ★ ⚠ same residue
IDS p.Ala346Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
IDS p.Ala85Asp Pathogenic/Likely pathogenic ★★ same condition
IDS p.Arg443Ter Pathogenic ★★ same condition
IDS p.Arg468Trp Pathogenic/Likely pathogenic ★★ same condition
IDS p.Arg493Pro Pathogenic/Likely pathogenic ★★ same condition
IDS p.Pro480Leu Pathogenic/Likely pathogenic ★★ same condition
IDS p.Pro86Leu 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/ids-p-his179 (accessed [today's date]).

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