Is IDS p.Val429Ile (c.1285G>A) pathogenic?

IDS p.Val429Ile (c.1285G>A) is classified Uncertain significance in IDS (ClinVar, Single submitter, 3 submitters; last evaluated 2025-01-21). AlphaMissense: likely benign (0.0714); Very rare (popmax 0.00176%, afr); Associated with mucopolysaccharidosis type 2.

What condition is associated with IDS p.Val429Ile (c.1285G>A)?

IDS p.Val429Ile (c.1285G>A) is associated with mucopolysaccharidosis type 2, epidermolysis bullosa simplex with nail dystrophy (ClinVar).

How common is IDS p.Val429Ile (c.1285G>A) in the general population?

IDS p.Val429Ile (c.1285G>A) is very rare (popmax 0.00176%, afr) (gnomAD).

How is Mucopolysaccharidosis type 2 inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about IDS p.Val429Ile (c.1285G>A)?

AlphaMissense predicts likely benign (score 0.0714) — an in-silico prediction, not a clinical call.

IDS p.Val429Ile

c.1285G>A · rs781916566 · VCV870146

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0714 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00176%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mucopolysaccharidosis type 2

Computational evidence

Protein change
AlphaMissense	0.0714	likely benign
REVEL	0.278	benign-leaning
SaProt	LLR -4.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.69	GERP -1.9
Regional constraint	o/e 0.78	unconstrained · MANE · 21 kb · p 5.6e-05 · regional, not allelic
Overall
CADD	1.278	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00176% African / African-American · 1/56,868 alleles

Filtering AF 0.000325% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000209%

Overall 0.000662% 8/1,208,260 alleles · very rare exomes 7/1,097,114 · genomes 1/111,146 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00176%	56,868
European (non-Finnish)	0.000783%	127,780

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.Val429Ile
Coding: c.1285G>A
MANE Select: NM_000202
dbSNP: rs781916566
Type: single nucleotide variant
Location: chrX:149483114 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB

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

Disease context

mucopolysaccharidosis type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: epidermolysis bullosa simplex with nail dystrophy

For Mucopolysaccharidosis type 2 (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Europe)

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-val429ile (accessed [today's date]).

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