Is IDS p.Pro469Arg (c.1406C>G) pathogenic?

IDS p.Pro469Arg (c.1406C>G) is classified Likely pathogenic in IDS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-07). AlphaMissense: likely pathogenic (0.8472); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with IDS p.Pro469Arg (c.1406C>G)?

IDS p.Pro469Arg (c.1406C>G) is associated with Inborn genetic diseases, mucopolysaccharidosis type 2 (ClinVar).

How common is IDS p.Pro469Arg (c.1406C>G) in the general population?

IDS p.Pro469Arg (c.1406C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IDS p.Pro469Arg (c.1406C>G)?

AlphaMissense predicts likely pathogenic (score 0.8472) — an in-silico prediction, not a clinical call.

IDS p.Pro469Arg

c.1406C>G · rs2123994360 · VCV2230429

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8472 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8472	likely pathogenic ✓ concordant with ClinVar
REVEL	0.761	pathogenic-leaning
SaProt	LLR -13.40	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 21 kb · p 5.6e-05 · regional, not allelic
Overall
CADD	24.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: IDS
Protein: p.Pro469Arg
Coding: c.1406C>G
MANE Select: NM_000202
dbSNP: rs2123994360
Type: single nucleotide variant
Location: chrX:149482993 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB
Residue 469: a UniProt-annotated variant site (in mps2; mild form); 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 2

Similar variants

IDS p.Pro469Leu Likely pathogenic ★★ same residue
IDS p.Pro469Ala Uncertain significance ★★ ⚠ same residue
IDS p.Pro469His Likely pathogenic ★ same residue
IDS p.Pro469_Ser470insTer Likely pathogenic ★ same residue
IDS p.Pro469Ser Uncertain significance ⚠ 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-pro469arg (accessed [today's date]).

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