Is IDS p.Asn325Ser (c.974A>G) pathogenic?

IDS p.Asn325Ser (c.974A>G) is classified Likely benign in IDS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-14). AlphaMissense: likely benign (0.0586); Ultra-rare (popmax 0.0267%, eas); Associated with mucopolysaccharidosis type 2.

What condition is associated with IDS p.Asn325Ser (c.974A>G)?

IDS p.Asn325Ser (c.974A>G) is associated with mucopolysaccharidosis type 2 (ClinVar).

How common is IDS p.Asn325Ser (c.974A>G) in the general population?

IDS p.Asn325Ser (c.974A>G) is ultra-rare (popmax 0.0267%, eas) (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.Asn325Ser (c.974A>G)?

AlphaMissense predicts likely benign (score 0.0586) — an in-silico prediction, not a clinical call.

IDS p.Asn325Ser

c.974A>G · rs202218431 · VCV3000159

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0586 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

mucopolysaccharidosis type 2

Computational evidence

Protein change
AlphaMissense	0.0586	likely benign
REVEL	0.31	indeterminate
SaProt	LLR -6.44	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.18	GERP -3.2, phastCons 0.021
Regional constraint	o/e 0.78	unconstrained · MANE · 21 kb · p 5.6e-05 · regional, not allelic
Overall
CADD	1.16	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 0.0267% East Asian · 9/33,761 alleles

Filtering AF 0.0139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0103%

Overall 0.000827% 10/1,209,467 alleles · ultra-rare exomes 9/1,097,381 · genomes 1/112,086 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0267%	3,751
Remaining individualsnot grpmax-eligible	0.0021%	47,608

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.Asn325Ser
Coding: c.974A>G
MANE Select: NM_000202
dbSNP: rs202218431
Type: single nucleotide variant
Location: chrX:149490346 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB
Residue 325: a turn

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 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
IDS c.104-2A>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-asn325ser (accessed [today's date]).

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