Is IDS p.Pro228= (c.684A>G) pathogenic?

IDS p.Pro228= (c.684A>G) is classified Conflicting classifications of pathogenicity in IDS (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-23). Ultra-rare (popmax 0.083%, eas); Associated with Inborn genetic diseases.

What condition is associated with IDS p.Pro228= (c.684A>G)?

IDS p.Pro228= (c.684A>G) is associated with Inborn genetic diseases, mucopolysaccharidosis type 3A, mucopolysaccharidosis type 2 (ClinVar).

How common is IDS p.Pro228= (c.684A>G) in the general population?

IDS p.Pro228= (c.684A>G) is ultra-rare (popmax 0.083%, eas) (gnomAD).

IDS p.Pro228=

c.684A>G · rs782561677 · VCV725382

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.083%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -2.8
Overall
CADD	0.286	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.083% East Asian · 28/33,755 alleles

Filtering AF 0.0589% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0508%

Overall 0.0024% 29/1,209,051 alleles · ultra-rare exomes 26/1,097,276 · genomes 3/111,775 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.083%	1,206
African / African-American	0.00175%	57,056

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.Pro228=
Coding: c.684A>G
MANE Select: NM_000202
dbSNP: rs782561677
Type: single nucleotide variant
Location: chrX:149498131 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB
Residue 228: a UniProt-annotated variant site (in mps2); a UniProt-annotated variant site (in mps2; severe form)

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 p.Pro228Gln Pathogenic/Likely pathogenic ★★ same residue
IDS p.Pro228Leu Pathogenic/Likely pathogenic ★★ same residue
IDS p.Pro228Ala Likely pathogenic ★ same residue
IDS p.Pro228Ser Likely pathogenic ★ same residue
IDS p.Pro228Thr 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

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-pro228 (accessed [today's date]).

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