Is IDS p.Val186Ala (c.557T>C) pathogenic?

IDS p.Val186Ala (c.557T>C) is classified Likely benign in IDS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-17). AlphaMissense: ambiguous (0.3791); Ultra-rare (popmax 0.0281%, sas); Associated with mucopolysaccharidosis type 2.

What condition is associated with IDS p.Val186Ala (c.557T>C)?

IDS p.Val186Ala (c.557T>C) is associated with mucopolysaccharidosis type 2 (ClinVar).

How common is IDS p.Val186Ala (c.557T>C) in the general population?

IDS p.Val186Ala (c.557T>C) is ultra-rare (popmax 0.0281%, 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.Val186Ala (c.557T>C)?

AlphaMissense predicts ambiguous (score 0.3791) — an in-silico prediction, not a clinical call.

IDS p.Val186Ala

c.557T>C · rs782007728 · VCV1569010

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3791 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0281%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

mucopolysaccharidosis type 2

Computational evidence

Protein change
AlphaMissense	0.3791	ambiguous
REVEL	0.699	pathogenic-leaning
SaProt	LLR -7.37	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.3, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 21 kb · p 5.6e-05 · regional, not allelic
Overall
CADD	22.6	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 0.0281% South Asian · 16/57,022 alleles

Filtering AF 0.0175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0143%

Overall 0.00157% 19/1,212,124 alleles · ultra-rare exomes 19/1,097,934 · genomes 0/114,190 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0281%	3,564
Remaining individualsnot grpmax-eligible	0.0063%	15,882

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.Val186Ala
Coding: c.557T>C
MANE Select: NM_000202
dbSNP: rs782007728
Type: single nucleotide variant
Location: chrX:149498258 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB
Residue 186: 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 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-val186ala (accessed [today's date]).

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