Is IDS p.Leu416= (c.1248G>T) pathogenic?

IDS p.Leu416= (c.1248G>T) is classified Likely benign in IDS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-16). Very rare (popmax 8.27e-05%); Associated with mucopolysaccharidosis type 2.

What condition is associated with IDS p.Leu416= (c.1248G>T)?

IDS p.Leu416= (c.1248G>T) is associated with mucopolysaccharidosis type 2 (ClinVar).

How common is IDS p.Leu416= (c.1248G>T) in the general population?

IDS p.Leu416= (c.1248G>T) is very rare (popmax 8.27e-05%) (gnomAD).

How is Mucopolysaccharidosis type 2 inherited?

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

IDS p.Leu416=

c.1248G>T · rs1306764023 · VCV3007329

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.27e-05%)

Conditions

mucopolysaccharidosis type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.012	GERP -2.3, phastCons 0.7
Overall
CADD	2.583	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.27e-05%

Overall 8.27e-05% 1/1,209,073 alleles · very rare exomes 0/1,097,857 · genomes 1/111,216 · 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.Leu416=
Coding: c.1248G>T
MANE Select: NM_000202
dbSNP: rs1306764023
Type: single nucleotide variant
Location: chrX:149483151 (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 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.Leu416_Gln417insHisLeuValGluLeuValSerLeuPheProThrLeuAlaGlyLeuAlaGlyLeu Likely 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
IDS c.1007-2A>C Pathogenic/Likely pathogenic ★★ same condition
IDS c.1007-8T>G Pathogenic/Likely pathogenic ★★ same condition
IDS c.103+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-leu416 (accessed [today's date]).

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