Is IDS p.Ala222= (c.666C>T) pathogenic?

IDS p.Ala222= (c.666C>T) is classified Benign in IDS (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-17). Rare (popmax 0.24%, eas); Associated with Inborn genetic diseases.

What condition is associated with IDS p.Ala222= (c.666C>T)?

IDS p.Ala222= (c.666C>T) is associated with Inborn genetic diseases, mucopolysaccharidosis type 3A, mucopolysaccharidosis type 2 (ClinVar).

How common is IDS p.Ala222= (c.666C>T) in the general population?

IDS p.Ala222= (c.666C>T) is rare (popmax 0.24%, eas) (gnomAD).

IDS p.Ala222=

c.666C>T · rs201588028 · VCV697822

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.24%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.6	GERP -2.9
Overall
CADD	4.783	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.24% East Asian · 81/33,747 alleles

Filtering AF 0.198% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.182%

Overall 0.0486% 588/1,209,697 alleles · rare exomes 547/1,097,898 · genomes 41/111,799 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.24%	417
Finnishnot grpmax-eligible	0.0902%	1,109
Remaining individualsnot grpmax-eligible	0.0504%	1,983
European (non-Finnish)	0.0487%	2,053
African / African-American	0.00525%	19,036
Admixed American	0.00218%	45,834
South Asian	0.00176%	56,807

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.Ala222=
Coding: c.666C>T
MANE Select: NM_000202
dbSNP: rs201588028
Type: single nucleotide variant
Location: chrX:149498149 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB
Residue 222: a β-strand

Full IDS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mucopolysaccharidosis type 3A mucopolysaccharidosis type 2

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-ala222 (accessed [today's date]).

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