Is IDS p.Arg48Cys (c.142C>T) pathogenic?

IDS p.Arg48Cys (c.142C>T) is classified Conflicting classifications of pathogenicity in IDS (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-03-11). AlphaMissense: ambiguous (0.4723); Absent from gnomAD v4.1; Associated with mucopolysaccharidosis type 2.

What condition is associated with IDS p.Arg48Cys (c.142C>T)?

IDS p.Arg48Cys (c.142C>T) is associated with mucopolysaccharidosis type 2 (ClinVar).

How common is IDS p.Arg48Cys (c.142C>T) in the general population?

IDS p.Arg48Cys (c.142C>T) is absent from gnomAD v4.1 (gnomAD).

How is Mucopolysaccharidosis type 2 inherited?

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

What do computational predictors say about IDS p.Arg48Cys (c.142C>T)?

AlphaMissense predicts ambiguous (score 0.4723) — an in-silico prediction, not a clinical call.

IDS p.Arg48Cys

c.142C>T · rs1412895796 · VCV2416195

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4723 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

mucopolysaccharidosis type 2

Computational evidence

Protein change
AlphaMissense	0.4723	ambiguous
REVEL	0.953	strongly pathogenic-leaning
SaProt	LLR -11.91	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 1.2, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 118 bp · p 0.0036 · regional, not allelic
Overall
CADD	29.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: IDS
Protein: p.Arg48Cys
Coding: c.142C>T
MANE Select: NM_000202
dbSNP: rs1412895796
Type: single nucleotide variant
Location: chrX:149504255 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB
Residue 48: a UniProt-annotated variant site (in mps2; mild form)

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.Arg48Pro Pathogenic ★★ same residue
IDS p.Arg48His 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
IDS c.1007-8T>G 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-arg48cys (accessed [today's date]).

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