Is IDS p.Leu178Val (c.532C>G) pathogenic?

IDS p.Leu178Val (c.532C>G) is classified Uncertain significance in IDS (ClinVar, Single submitter, 2 submitters; last evaluated 2024-07-22). AlphaMissense: likely benign (0.1362); Very rare (popmax 0.000224%, nfe); Associated with mucopolysaccharidosis type 2.

What condition is associated with IDS p.Leu178Val (c.532C>G)?

IDS p.Leu178Val (c.532C>G) is associated with mucopolysaccharidosis type 2, mucopolysaccharidosis type 3A (ClinVar).

How common is IDS p.Leu178Val (c.532C>G) in the general population?

IDS p.Leu178Val (c.532C>G) is very rare (popmax 0.000224%, 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.Leu178Val (c.532C>G)?

AlphaMissense predicts likely benign (score 0.1362) — an in-silico prediction, not a clinical call.

IDS p.Leu178Val

c.532C>G · VCV3704749

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1362 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000224%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mucopolysaccharidosis type 2

Computational evidence

Protein change
AlphaMissense	0.1362	likely benign
REVEL	0.758	pathogenic-leaning
SaProt	LLR -9.63	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.3, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 21 kb · p 5.6e-05 · regional, not allelic
Overall
CADD	23.7	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 0.000224% European (non-Finnish) · 2/894,541 alleles

Filtering AF 3.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000165% 2/1,210,933 alleles · very rare exomes 2/1,096,980 · genomes 0/113,953 · 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.Leu178Val
Coding: c.532C>G
MANE Select: NM_000202
Type: single nucleotide variant
Location: chrX:149498283 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB

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.Leu178= 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-leu178val (accessed [today's date]).

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