Is IDS p.Cys84= (c.252C>T) pathogenic?

IDS p.Cys84= (c.252C>T) is classified Likely benign in IDS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-22). Very rare (popmax 0.00182%, afr); Associated with mucopolysaccharidosis type 2.

What condition is associated with IDS p.Cys84= (c.252C>T)?

IDS p.Cys84= (c.252C>T) is associated with mucopolysaccharidosis type 2 (ClinVar).

How common is IDS p.Cys84= (c.252C>T) in the general population?

IDS p.Cys84= (c.252C>T) is very rare (popmax 0.00182%, 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.Cys84=

c.252C>T · rs1557340286 · VCV1137279

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00182%, 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 -5.3	GERP -2.1
Overall
CADD	1.445	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00182% African / African-American · 1/54,959 alleles

Filtering AF 4e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.5e-05%

Overall 0.000356% 4/1,124,121 alleles · very rare exomes 3/1,013,538 · genomes 1/110,583 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00223%	44,755
African / African-Americangrpmax	0.00182%	54,959
European (non-Finnish)	0.000241%	415,124

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Cys84=
Coding: c.252C>T
MANE Select: NM_000202
dbSNP: rs1557340286
Type: single nucleotide variant
Location: chrX:149503478 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB
Residue 84: a modified residue (3-oxoalanine (cys)); an α-helix; an active site; a binding site

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.Cys84Ter Pathogenic ★★ same residue
IDS p.Cys84Trp Pathogenic/Likely pathogenic ★★ same residue
IDS p.Cys84Ser Pathogenic ★ ⚠ same residue
IDS p.Cys84Tyr Likely pathogenic ★ 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

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-cys84 (accessed [today's date]).

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