Is IDS p.Pro86Leu (c.257C>T) pathogenic?

IDS p.Pro86Leu (c.257C>T) is classified Pathogenic in IDS (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-06-20). AlphaMissense: likely pathogenic (0.9069); Absent from gnomAD v4.1; Associated with mucopolysaccharidosis type 2.

What condition is associated with IDS p.Pro86Leu (c.257C>T)?

IDS p.Pro86Leu (c.257C>T) is associated with mucopolysaccharidosis type 2, mucopolysaccharidosis type 3A (ClinVar).

How common is IDS p.Pro86Leu (c.257C>T) in the general population?

IDS p.Pro86Leu (c.257C>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.Pro86Leu (c.257C>T)?

AlphaMissense predicts likely pathogenic (score 0.9069) — an in-silico prediction, not a clinical call.

IDS p.Pro86Leu

c.257C>T · rs1557340280 · VCV527322

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely pathogenic

0.9069 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mucopolysaccharidosis type 2

Computational evidence

Protein change
AlphaMissense	0.9069	likely pathogenic ✓ concordant with ClinVar
REVEL	0.983	strongly pathogenic-leaning
SaProt	LLR -16.76	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.59	acceptor gain · deltas
Pangolin	Δ0.50	gain · loss 0.31 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 8.3	GERP 1.1, phastCons 1
Regional constraint	o/e 0.07	constrained · MANE · 819 bp · p 6.4e-10 · regional, not allelic
Overall
CADD	33.0	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.Pro86Leu
Coding: c.257C>T
MANE Select: NM_000202
dbSNP: rs1557340280
Type: single nucleotide variant
Location: chrX:149503473 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB
Residue 86: an α-helix; a UniProt-annotated variant site (in mps2; intermediate to severe forms); a UniProt-annotated variant site (in mps2); a UniProt-annotated variant site (in mps2; severe 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

Also linked: mucopolysaccharidosis type 3A

For Mucopolysaccharidosis type 2 (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

IDS p.Pro86Arg Pathogenic ★★ same residue
IDS p.Pro86Gln Pathogenic ★ same residue
IDS p.Pro86= Likely benign ★ same residue
IDS p.Pro86fs 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-pro86leu (accessed [today's date]).

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