Is IDS p.Leu41= (c.123C>G) pathogenic?

IDS p.Leu41= (c.123C>G) is classified Benign/Likely benign in IDS (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-24). Rare (popmax 0.338%, afr); Associated with mucopolysaccharidosis type 2.

What condition is associated with IDS p.Leu41= (c.123C>G)?

IDS p.Leu41= (c.123C>G) is associated with mucopolysaccharidosis type 2 (ClinVar).

How common is IDS p.Leu41= (c.123C>G) in the general population?

IDS p.Leu41= (c.123C>G) is rare (popmax 0.338%, afr) (gnomAD).

How is Mucopolysaccharidosis type 2 inherited?

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

IDS p.Leu41=

c.123C>G · rs146904022 · VCV590202

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.338%, afr)

Conditions

mucopolysaccharidosis type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.065	GERP -2.6, phastCons 0.91
Overall
CADD	1.432	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.338% African / African-American · 193/57,150 alleles

Filtering AF 0.299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.284%

Overall 0.0193% 233/1,207,167 alleles · rare exomes 108/1,094,937 · genomes 125/112,230 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.338%	296
Admixed American	0.0657%	1,521
Remaining individualsnot grpmax-eligible	0.021%	4,752

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.Leu41=
Coding: c.123C>G
MANE Select: NM_000202
dbSNP: rs146904022
Type: single nucleotide variant
Location: chrX:149504274 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB
Residue 41: a β-strand; a UniProt-annotated variant site (in mps2; mild form; increase in enzyme activity observed in transfected cells); a UniProt-annotated variant site (in mps2; intermediate 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.Leu41Pro Likely pathogenic ★ same residue
IDS p.Leu41del Conflicting classifications of pathogenicity ★ 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
IDS c.1007-8T>G 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-leu41 (accessed [today's date]).

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