Is IDS p.Pro251= (c.753C>T) pathogenic?

IDS p.Pro251= (c.753C>T) is classified Benign/Likely benign in IDS (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-02-12). Very rare (popmax 0.00839%, nfe); Associated with Inborn genetic diseases.

What condition is associated with IDS p.Pro251= (c.753C>T)?

IDS p.Pro251= (c.753C>T) is associated with Inborn genetic diseases, mucopolysaccharidosis type 2 (ClinVar).

How common is IDS p.Pro251= (c.753C>T) in the general population?

IDS p.Pro251= (c.753C>T) is very rare (popmax 0.00839%, nfe) (gnomAD).

IDS p.Pro251=

c.753C>T · rs782051908 · VCV589014

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00839%, nfe)

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 -1.3	GERP -3.2
Overall
CADD	0.623	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00839% European (non-Finnish) · 75/894,452 alleles

Filtering AF 0.00685% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00625%

Overall 0.00653% 79/1,209,026 alleles · very rare exomes 73/1,097,042 · genomes 6/111,984 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00839%	11,926
East Asian	0.00296%	33,765
Remaining individualsnot grpmax-eligible	0.0021%	47,531
South Asian	0.00176%	56,818
African / African-American	0.00175%	57,147

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.Pro251=
Coding: c.753C>T
MANE Select: NM_000202
dbSNP: rs782051908
Type: single nucleotide variant
Location: chrX:149496472 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB

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 2

Similar variants

IDS p.Pro251_Asp252insTer 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
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-pro251 (accessed [today's date]).

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