Is IDS p.Thr6Ala (c.16A>G) pathogenic?

IDS p.Thr6Ala (c.16A>G) is classified Uncertain significance in IDS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-05-01). AlphaMissense: likely benign (0.0571); Absent from gnomAD v4.1; Associated with mucopolysaccharidosis type 3A.

What condition is associated with IDS p.Thr6Ala (c.16A>G)?

IDS p.Thr6Ala (c.16A>G) is associated with mucopolysaccharidosis type 3A (ClinVar).

How common is IDS p.Thr6Ala (c.16A>G) in the general population?

IDS p.Thr6Ala (c.16A>G) is absent from gnomAD v4.1 (gnomAD).

How is Mucopolysaccharidosis type 3 inherited?

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

What do computational predictors say about IDS p.Thr6Ala (c.16A>G)?

AlphaMissense predicts likely benign (score 0.0571) — an in-silico prediction, not a clinical call.

IDS p.Thr6Ala

c.16A>G · VCV4069632

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0571 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

mucopolysaccharidosis type 3A

Computational evidence

Protein change
AlphaMissense	0.0571	likely benign
REVEL	0.406	indeterminate
SaProt	LLR -5.08	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -2, phastCons 0.036
Regional constraint	o/e 1.34	unconstrained · MANE · 858 bp · p 0.049 · regional, not allelic
Overall
CADD	1.064	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

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.Thr6Ala
Coding: c.16A>G
MANE Select: NM_000202
Type: single nucleotide variant
Location: chrX:149505122 (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 3A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Mucopolysaccharidosis type 3 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Brazil)

Similar variants

IDS p.Thr6= Likely benign ★ same residue
IDS p.Ala346Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
IDS p.Ala85Asp Pathogenic/Likely pathogenic ★★ same condition
IDS p.Arg443Ter Pathogenic ★★ same condition
IDS p.Arg468Trp Pathogenic/Likely pathogenic ★★ same condition
IDS p.Arg493Pro Pathogenic/Likely pathogenic ★★ same condition
IDS p.Pro480Leu Pathogenic/Likely pathogenic ★★ same condition
IDS p.Pro86Leu 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-thr6ala (accessed [today's date]).

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