Is IDS p.Leu11Pro (c.32T>C) pathogenic?

IDS p.Leu11Pro (c.32T>C) is classified Uncertain significance in IDS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-05-08). AlphaMissense: likely benign (0.1028); Very rare (popmax 0.00707%, sas); Associated with mucopolysaccharidosis type 3A.

What condition is associated with IDS p.Leu11Pro (c.32T>C)?

IDS p.Leu11Pro (c.32T>C) is associated with mucopolysaccharidosis type 3A (ClinVar).

How common is IDS p.Leu11Pro (c.32T>C) in the general population?

IDS p.Leu11Pro (c.32T>C) is very rare (popmax 0.00707%, sas) (gnomAD).

How is Mucopolysaccharidosis type 3 inherited?

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

What do computational predictors say about IDS p.Leu11Pro (c.32T>C)?

AlphaMissense predicts likely benign (score 0.1028) — an in-silico prediction, not a clinical call.

IDS p.Leu11Pro

c.32T>C · VCV4069631

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1028 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00707%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

mucopolysaccharidosis type 3A

Computational evidence

Protein change
AlphaMissense	0.1028	likely benign
REVEL	0.561	indeterminate
SaProt	LLR -7.15	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 5.6	GERP 1.2, phastCons 0.93
Regional constraint	o/e 1.34	unconstrained · MANE · 858 bp · p 0.049 · regional, not allelic
Overall
CADD	17.24	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00707% South Asian · 4/56,556 alleles

Filtering AF 0.00235% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00141%

Overall 0.000332% 4/1,203,735 alleles · very rare exomes 4/1,090,195 · genomes 0/113,540 · 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.Leu11Pro
Coding: c.32T>C
MANE Select: NM_000202
Type: single nucleotide variant
Location: chrX:149505106 (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 3A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Mucopolysaccharidosis type 3 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Brazil)

Similar variants

IDS p.Leu11Phe Conflicting classifications of pathogenicity ★ ⚠ same residue
IDS p.Leu11= Likely benign ★ same residue
IDS p.Ala346Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
IDS p.Ala85Asp Pathogenic/Likely pathogenic ★★ same condition
IDS p.Arg443Ter Pathogenic ★★ same condition
IDS p.Arg468Trp Pathogenic/Likely pathogenic ★★ same condition
IDS p.Arg493Pro Pathogenic/Likely pathogenic ★★ same condition
IDS p.Pro480Leu 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-leu11pro (accessed [today's date]).

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