Is IDS p.Ile328Val (c.982A>G) pathogenic?

IDS p.Ile328Val (c.982A>G) is classified Likely benign in IDS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-04). AlphaMissense: likely benign (0.067); Ultra-rare (popmax 0.0193%, sas); Associated with mucopolysaccharidosis type 2.

What condition is associated with IDS p.Ile328Val (c.982A>G)?

IDS p.Ile328Val (c.982A>G) is associated with mucopolysaccharidosis type 2 (ClinVar).

How common is IDS p.Ile328Val (c.982A>G) in the general population?

IDS p.Ile328Val (c.982A>G) is ultra-rare (popmax 0.0193%, sas) (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.Ile328Val (c.982A>G)?

AlphaMissense predicts likely benign (score 0.067) — an in-silico prediction, not a clinical call.

IDS p.Ile328Val

c.982A>G · rs782156020 · VCV1157535

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.067 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0193%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

mucopolysaccharidosis type 2

Computational evidence

Protein change
AlphaMissense	0.067	likely benign
REVEL	0.361	indeterminate
SaProt	LLR -7.36	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.29	GERP -0.66, phastCons 0.072
Regional constraint	o/e 0.78	unconstrained · MANE · 21 kb · p 5.6e-05 · regional, not allelic
Overall
CADD	6.189	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 0.0193% South Asian · 11/57,008 alleles

Filtering AF 0.0108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00833%

Overall 0.000991% 12/1,211,189 alleles · ultra-rare exomes 12/1,097,230 · genomes 0/113,959 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0193%	5,183
Remaining individualsnot grpmax-eligible	0.0021%	47,626

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.Ile328Val
Coding: c.982A>G
MANE Select: NM_000202
dbSNP: rs782156020
Type: single nucleotide variant
Location: chrX:149490338 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB
Residue 328: a β-strand

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.Ile328_Thr332del 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-ile328val (accessed [today's date]).

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