Is IDS p.Pro261fs (c.782del) pathogenic?

IDS p.Pro261fs (c.782del) is classified Pathogenic in IDS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-07). Very rare (popmax 0.000112%, nfe); Associated with mucopolysaccharidosis type 2.

What condition is associated with IDS p.Pro261fs (c.782del)?

IDS p.Pro261fs (c.782del) is associated with mucopolysaccharidosis type 2 (ClinVar).

How common is IDS p.Pro261fs (c.782del) in the general population?

IDS p.Pro261fs (c.782del) is very rare (popmax 0.000112%, nfe) (gnomAD).

How is Mucopolysaccharidosis type 2 inherited?

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

IDS p.Pro261fs

c.782del · rs2520851440 · VCV2737386

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Conditions

mucopolysaccharidosis type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 6 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.094	GERP -3.2, phastCons 0.012

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/892,962 alleles

Overall 8.27e-05% 1/1,208,974 alleles · very rare exomes 1/1,095,127 · genomes 0/113,847 · joint denominator

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.Pro261fs
Coding: c.782del
MANE Select: NM_000202
dbSNP: rs2520851440
Type: Deletion
Location: chrX:149496443 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB
Residue 261: an α-helix

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.Pro261Ser Uncertain significance ★★ ⚠ same residue
IDS p.Pro261Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
IDS p.Pro261= Likely benign ★ same residue
IDS p.Pro261Thr Benign ★ same residue
IDS c.418+1_418+4del Pathogenic ★★ same condition
IDS p.Arg468fs Pathogenic/Likely pathogenic ★★ same condition
IDS p.Arg8fs Pathogenic ★★ same condition
IDS p.Arg96del 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-pro261fs (accessed [today's date]).

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