Is IDS p.Asp35Gly (c.104A>G) pathogenic?

IDS p.Asp35Gly (c.104A>G) is classified Conflicting classifications of pathogenicity in IDS (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.0639); Ultra-rare (popmax 0.0248%, nfe); Associated with mucopolysaccharidosis type 2.

What condition is associated with IDS p.Asp35Gly (c.104A>G)?

IDS p.Asp35Gly (c.104A>G) is associated with mucopolysaccharidosis type 2, mucopolysaccharidosis type 3A (ClinVar).

How common is IDS p.Asp35Gly (c.104A>G) in the general population?

IDS p.Asp35Gly (c.104A>G) is ultra-rare (popmax 0.0248%, nfe) (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.Asp35Gly (c.104A>G)?

AlphaMissense predicts likely benign (score 0.0639) — an in-silico prediction, not a clinical call.

IDS p.Asp35Gly

c.104A>G · rs144081417 · VCV195036

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0639 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0248%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

mucopolysaccharidosis type 2

Computational evidence

Protein change
AlphaMissense	0.0639	likely benign
REVEL	0.416	indeterminate
SaProt	LLR -1.33	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.44	GERP -2.3, phastCons 0.19
Regional constraint	o/e 1.34	unconstrained · MANE · 858 bp · p 0.049 · regional, not allelic
Overall
CADD	11.55	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

Grpmax group 0.0248% European (non-Finnish) · 221/892,039 alleles

Filtering AF 0.0221% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.021%

Overall 0.0203% 245/1,204,874 alleles · ultra-rare exomes 223/1,092,865 · genomes 22/112,009 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0248%	4,036
Middle Eastern	0.0229%	4,358
Remaining individualsnot grpmax-eligible	0.0211%	4,741
Finnishnot grpmax-eligible	0.0194%	5,148
Ashkenazi Jewishnot grpmax-eligible	0.00456%	21,910
Admixed American	0.0044%	22,718
South Asian	0.00178%	56,060

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.Asp35Gly
Coding: c.104A>G
MANE Select: NM_000202
dbSNP: rs144081417
Type: single nucleotide variant
Location: chrX:149504293 (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: mucopolysaccharidosis type 3A

For Mucopolysaccharidosis type 2 (Orphanet):

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

Similar variants

IDS p.Asp35His Likely pathogenic ★★ ⚠ same residue
IDS p.Asp35fs Pathogenic ★ same residue
IDS p.Asp35Tyr Likely pathogenic ★ ⚠ same residue
IDS p.Asp35Val 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
IDS c.1007-1G>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-asp35gly (accessed [today's date]).

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