Is IDS p.Ile42= (c.126C>T) pathogenic?

IDS p.Ile42= (c.126C>T) is classified Benign/Likely benign in IDS (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-24). Rare (popmax 0.342%, afr); Associated with mucopolysaccharidosis type 2.

What condition is associated with IDS p.Ile42= (c.126C>T)?

IDS p.Ile42= (c.126C>T) is associated with mucopolysaccharidosis type 2 (ClinVar).

How common is IDS p.Ile42= (c.126C>T) in the general population?

IDS p.Ile42= (c.126C>T) is rare (popmax 0.342%, afr) (gnomAD).

How is Mucopolysaccharidosis type 2 inherited?

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

IDS p.Ile42=

c.126C>T · rs146963087 · VCV595868

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.342%, afr)

Conditions

mucopolysaccharidosis type 2

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 3.1	GERP -0.81, phastCons 1
Overall
CADD	8.639	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.342% African / African-American · 193/56,467 alleles

Filtering AF 0.302% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.287%

Overall 0.0193% 233/1,204,651 alleles · rare exomes 108/1,094,484 · genomes 125/110,167 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.342%	293
Admixed American	0.066%	1,515
Remaining individualsnot grpmax-eligible	0.0211%	4,745

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.Ile42=
Coding: c.126C>T
MANE Select: NM_000202
dbSNP: rs146963087
Type: single nucleotide variant
Location: chrX:149504271 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB
Residue 42: a β-strand

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

Disease context

mucopolysaccharidosis type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Mucopolysaccharidosis type 2 (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

IDS p.Ile42Val Uncertain significance ★ ⚠ same residue
IDS p.Ile42fs Pathogenic ★ same residue
IDS p.Ile42Met Uncertain significance ★★ ⚠ same residue
IDS c.1006+1G>C Pathogenic ★★ same condition
IDS c.1006+1G>T Pathogenic ★★ same condition
IDS c.1007-133A>G Likely pathogenic ★★ same condition
IDS c.1007-1G>A Pathogenic ★★ same condition
IDS c.1007-2A>C Pathogenic/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/ids-p-ile42 (accessed [today's date]).

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