Is IDS p.Leu102Pro (c.305T>C) pathogenic?

IDS p.Leu102Pro (c.305T>C) is classified Likely pathogenic in IDS (ClinVar, Single submitter, 2 submitters; last evaluated 2024-06-07). AlphaMissense: likely pathogenic (0.9876); Absent from gnomAD v4.1; Associated with mucopolysaccharidosis type 2.

What condition is associated with IDS p.Leu102Pro (c.305T>C)?

IDS p.Leu102Pro (c.305T>C) is associated with mucopolysaccharidosis type 2 (ClinVar).

How common is IDS p.Leu102Pro (c.305T>C) in the general population?

IDS p.Leu102Pro (c.305T>C) 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.Leu102Pro (c.305T>C)?

AlphaMissense predicts likely pathogenic (score 0.9876) — an in-silico prediction, not a clinical call.

IDS p.Leu102Pro

c.305T>C · rs1557340261 · VCV1342151

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9876 · 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	0.9876	likely pathogenic ✓ concordant with ClinVar · top 2% in IDS
REVEL	0.968	strongly pathogenic-leaning
SaProt	LLR -15.04	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9	GERP 1.1, phastCons 1
Regional constraint	o/e 0.07	constrained · MANE · 819 bp · p 6.4e-10 · regional, not allelic
Overall
CADD	28.0	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.Leu102Pro
Coding: c.305T>C
MANE Select: NM_000202
dbSNP: rs1557340261
Type: single nucleotide variant
Location: chrX:149503425 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB
Residue 102: 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.Leu102Arg Likely pathogenic ★ same residue
IDS p.Leu102= Likely benign ★ same residue
IDS p.Leu102fs Pathogenic ★ same residue
IDS p.Leu102Gln 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

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-leu102pro (accessed [today's date]).

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