Is IDS p.Arg88= (c.264C>T) pathogenic?

IDS p.Arg88= (c.264C>T) is classified Likely benign in IDS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-30). Ultra-rare (popmax 0.0282%, mid); Associated with mucopolysaccharidosis type 2.

What condition is associated with IDS p.Arg88= (c.264C>T)?

IDS p.Arg88= (c.264C>T) is associated with mucopolysaccharidosis type 2 (ClinVar).

How common is IDS p.Arg88= (c.264C>T) in the general population?

IDS p.Arg88= (c.264C>T) is ultra-rare (popmax 0.0282%, mid) (gnomAD).

How is Mucopolysaccharidosis type 2 inherited?

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

IDS p.Arg88=

c.264C>T · rs375362189 · VCV1625311

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0282%, mid)

Conditions

mucopolysaccharidosis type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.28	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -7.2	GERP -2.2
Overall
CADD	1.056	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0282% Middle Eastern · 1/3,544 alleles

Filtering AF 0.00243% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00127%

Overall 0.000784% 9/1,148,197 alleles · ultra-rare exomes 9/1,035,326 · genomes 0/112,871 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0282%	3,544
East Asian	0.00918%	10,893
Remaining individualsnot grpmax-eligible	0.0088%	11,370
European (non-Finnish)	0.000118%	849,452

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.Arg88=
Coding: c.264C>T
MANE Select: NM_000202
dbSNP: rs375362189
Type: single nucleotide variant
Location: chrX:149503466 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB
Residue 88: an α-helix; a UniProt-annotated variant site (in mps2; severe form); a UniProt-annotated variant site (in mps2; intermediate/severe form; higher affinity for the artificial substrate; poor transport to lysosomes); a UniProt-annotated variant site (in mps2; severe form; total absence of residual activity; poor transport to lysosomes)

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.Arg88Cys Pathogenic ★★ same residue
IDS p.Arg88His Pathogenic/Likely pathogenic ★★ same residue
IDS p.Arg88Gly Pathogenic ★ same residue
IDS p.Arg88Leu Pathogenic ★ same residue
IDS p.Arg88Pro Pathogenic ★ same residue
IDS p.Arg88Ser Pathogenic ★ same residue
IDS c.1006+1G>C Pathogenic ★★ same condition
IDS c.1006+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/ids-p-arg88 (accessed [today's date]).

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