Is IDS p.Arg445Cys (c.1333C>T) pathogenic?

IDS p.Arg445Cys (c.1333C>T) is classified Likely benign in IDS (ClinVar, Single submitter, 2 submitters; last evaluated 2025-03-16). AlphaMissense: likely benign (0.0842); Very rare (popmax 0.00531%, sas); Associated with mucopolysaccharidosis type 2.

What condition is associated with IDS p.Arg445Cys (c.1333C>T)?

IDS p.Arg445Cys (c.1333C>T) is associated with mucopolysaccharidosis type 2 (ClinVar).

How common is IDS p.Arg445Cys (c.1333C>T) in the general population?

IDS p.Arg445Cys (c.1333C>T) is very rare (popmax 0.00531%, sas) (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.Arg445Cys (c.1333C>T)?

AlphaMissense predicts likely benign (score 0.0842) — an in-silico prediction, not a clinical call.

IDS p.Arg445Cys

c.1333C>T · rs929376875 · VCV2165769

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0842 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00531%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

mucopolysaccharidosis type 2

Computational evidence

Protein change
AlphaMissense	0.0842	likely benign
REVEL	0.451	indeterminate
SaProt	LLR -8.99	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.98	GERP -1.6, phastCons 0.031
Regional constraint	o/e 0.78	unconstrained · MANE · 21 kb · p 5.6e-05 · regional, not allelic
Overall
CADD	13.43	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

Grpmax group 0.00531% South Asian · 3/56,493 alleles

Filtering AF 0.00141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000691%

Overall 0.000913% 11/1,205,152 alleles · very rare exomes 10/1,093,574 · genomes 1/111,578 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00531%	18,831
East Asian	0.00297%	33,674
Admixed American	0.00219%	45,569
African / African-American	0.00176%	56,938
European (non-Finnish)	0.000561%	178,349

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.Arg445Cys
Coding: c.1333C>T
MANE Select: NM_000202
dbSNP: rs929376875
Type: single nucleotide variant
Location: chrX:149483066 (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 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.Arg445His Conflicting classifications of pathogenicity ★ ⚠ same residue
IDS p.Arg445= Likely benign ★ same residue
IDS p.Arg445Ser 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-arg445cys (accessed [today's date]).

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