Is IDS p.Arg294Gln (c.881G>A) pathogenic?

IDS p.Arg294Gln (c.881G>A) is classified Conflicting classifications of pathogenicity in IDS (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-07-08). AlphaMissense: likely benign (0.0702); Ultra-rare (popmax 0.028%, nfe); Associated with mucopolysaccharidosis type 2.

What condition is associated with IDS p.Arg294Gln (c.881G>A)?

IDS p.Arg294Gln (c.881G>A) is associated with mucopolysaccharidosis type 2, mucopolysaccharidosis type 3A (ClinVar).

How common is IDS p.Arg294Gln (c.881G>A) in the general population?

IDS p.Arg294Gln (c.881G>A) is ultra-rare (popmax 0.028%, nfe) (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.Arg294Gln (c.881G>A)?

AlphaMissense predicts likely benign (score 0.0702) — an in-silico prediction, not a clinical call.

IDS p.Arg294Gln

c.881G>A · rs782445506 · VCV767325

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0702 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.028%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

mucopolysaccharidosis type 2

Computational evidence

Protein change
AlphaMissense	0.0702	likely benign
REVEL	0.476	indeterminate
SaProt	LLR -8.92	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.80	acceptor gain · deltas
Pangolin	Δ0.27	gain · loss 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.77	GERP -1.1, phastCons 0.24
Regional constraint	o/e 0.78	unconstrained · MANE · 21 kb · p 5.6e-05 · regional, not allelic
Overall
CADD	24.4	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

Grpmax group 0.028% European (non-Finnish) · 250/894,376 alleles

Filtering AF 0.0251% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.024%

Overall 0.0218% 263/1,208,556 alleles · ultra-rare exomes 251/1,097,250 · genomes 12/111,306 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.028%	3,578
Remaining individualsnot grpmax-eligible	0.0147%	6,798
South Asian	0.00528%	18,923
Admixed American	0.00219%	45,711
Finnishnot grpmax-eligible	0.00215%	46,405
African / African-American	0.00176%	56,925

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.Arg294Gln
Coding: c.881G>A
MANE Select: NM_000202
dbSNP: rs782445506
Type: single nucleotide variant
Location: chrX:149490439 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB
Residue 294: an α-helix

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

Also linked: mucopolysaccharidosis type 3A

For Mucopolysaccharidosis type 2 (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

IDS p.Arg294Trp 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
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-arg294gln (accessed [today's date]).

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