Is IDS p.Pro423= (c.1269C>T) pathogenic?

IDS p.Pro423= (c.1269C>T) is classified Benign/Likely benign in IDS (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). Low-frequency (popmax 1.89%, afr); Associated with Inborn genetic diseases.

What condition is associated with IDS p.Pro423= (c.1269C>T)?

IDS p.Pro423= (c.1269C>T) is associated with Inborn genetic diseases, mucopolysaccharidosis type 2 (ClinVar).

How common is IDS p.Pro423= (c.1269C>T) in the general population?

IDS p.Pro423= (c.1269C>T) is low-frequency (popmax 1.89%, afr) (gnomAD).

IDS p.Pro423=

c.1269C>T · rs61736890 · VCV590249

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.89%, afr)

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	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.2	GERP -3.2
Overall
CADD	0.366	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.89% African / African-American · 1,073/56,873 alleles

Filtering AF 1.79% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.76%

Overall 0.103% 1,248/1,208,327 alleles · low-frequency exomes 684/1,097,261 · genomes 564/111,066 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.89%	53
Middle Eastern	0.254%	394
Remaining individualsnot grpmax-eligible	0.185%	540
Admixed American	0.0944%	1,060
South Asian	0.0247%	4,049
European (non-Finnish)	0.00212%	47,076

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.Pro423=
Coding: c.1269C>T
MANE Select: NM_000202
dbSNP: rs61736890
Type: single nucleotide variant
Location: chrX:149483130 (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.Pro423Ser Likely pathogenic ★ ⚠ same residue
IDS p.Pro423Leu 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

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-pro423 (accessed [today's date]).

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