Is IDS p.Gln465Arg (c.1394A>G) pathogenic?

IDS p.Gln465Arg (c.1394A>G) is classified Uncertain significance in IDS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-04-24). AlphaMissense: likely pathogenic (0.8457); Absent from gnomAD v4.1; Associated with mucopolysaccharidosis type 3A.

What condition is associated with IDS p.Gln465Arg (c.1394A>G)?

IDS p.Gln465Arg (c.1394A>G) is associated with mucopolysaccharidosis type 3A (ClinVar).

How common is IDS p.Gln465Arg (c.1394A>G) in the general population?

IDS p.Gln465Arg (c.1394A>G) is absent from gnomAD v4.1 (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.Gln465Arg (c.1394A>G)?

AlphaMissense predicts likely pathogenic (score 0.8457) — an in-silico prediction, not a clinical call.

IDS p.Gln465Arg

c.1394A>G · VCV4069633

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8457 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mucopolysaccharidosis type 3A

Computational evidence

Protein change
AlphaMissense	0.8457	likely pathogenic
REVEL	0.774	moderately pathogenic-leaning
SaProt	LLR -15.07	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 21 kb · p 5.6e-05 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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.Gln465Arg
Coding: c.1394A>G
MANE Select: NM_000202
Type: single nucleotide variant
Location: chrX:149483005 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB
Residue 465: a UniProt-annotated variant site (in mps2; severe form); a β-strand

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.Gln465Ter Pathogenic ★★ same residue
IDS p.Gln465Leu Likely pathogenic ★ same residue
IDS p.Gln465Lys Likely pathogenic ★ same residue
IDS p.Gln465Pro Likely pathogenic ★ same residue
IDS p.Gln465= 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

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-gln465arg (accessed [today's date]).

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