Is IDS p.Asp399Val (c.1196A>T) pathogenic?

IDS p.Asp399Val (c.1196A>T) is classified Likely benign in IDS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-13). AlphaMissense: likely benign (0.1199); Very rare (popmax 0.00217%, amr); Associated with mucopolysaccharidosis type 2.

What condition is associated with IDS p.Asp399Val (c.1196A>T)?

IDS p.Asp399Val (c.1196A>T) is associated with mucopolysaccharidosis type 2 (ClinVar).

How common is IDS p.Asp399Val (c.1196A>T) in the general population?

IDS p.Asp399Val (c.1196A>T) is very rare (popmax 0.00217%, amr) (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.Asp399Val (c.1196A>T)?

AlphaMissense predicts likely benign (score 0.1199) — an in-silico prediction, not a clinical call.

IDS p.Asp399Val

c.1196A>T · rs1557337663 · VCV2002774

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1199 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00217%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

mucopolysaccharidosis type 2

Computational evidence

Protein change
AlphaMissense	0.1199	likely benign
REVEL	0.388	indeterminate
SaProt	LLR -5.44	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 4.1	GERP 0.29, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 21 kb · p 5.6e-05 · regional, not allelic
Overall
CADD	16.7	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 0.00217% Admixed American · 1/46,035 alleles

Overall 8.27e-05% 1/1,209,267 alleles · very rare exomes 1/1,095,916 · genomes 0/113,351 · 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.Asp399Val
Coding: c.1196A>T
MANE Select: NM_000202
dbSNP: rs1557337663
Type: single nucleotide variant
Location: chrX:149483203 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB
Residue 399: 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.Asp399= Likely benign ★ 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-asp399val (accessed [today's date]).

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