Is IDS p.Ser71Ile (c.212G>T) pathogenic?

IDS p.Ser71Ile (c.212G>T) is classified Likely pathogenic in IDS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-07). AlphaMissense: likely pathogenic (0.9304); Absent from gnomAD v4.1; Associated with mucopolysaccharidosis type 2.

What condition is associated with IDS p.Ser71Ile (c.212G>T)?

IDS p.Ser71Ile (c.212G>T) is associated with mucopolysaccharidosis type 2 (ClinVar).

How common is IDS p.Ser71Ile (c.212G>T) in the general population?

IDS p.Ser71Ile (c.212G>T) is absent from gnomAD v4.1 (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.Ser71Ile (c.212G>T)?

AlphaMissense predicts likely pathogenic (score 0.9304) — an in-silico prediction, not a clinical call.

IDS p.Ser71Ile

c.212G>T · rs113993954 · VCV996541

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9304 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mucopolysaccharidosis type 2

Computational evidence

Protein change
AlphaMissense	0.9304	likely pathogenic ✓ concordant with ClinVar · top 10% in IDS
REVEL	0.94	strongly pathogenic-leaning
SaProt	LLR -16.40	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.5	GERP 1.4, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 118 bp · p 0.0036 · regional, not allelic
Overall
CADD	29.1	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.Ser71Ile
Coding: c.212G>T
MANE Select: NM_000202
dbSNP: rs113993954
Type: single nucleotide variant
Location: chrX:149504185 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB
Residue 71: a β-strand; a UniProt-annotated variant site (in mps2; mild form); a UniProt-annotated variant site (in mps2; severe form)

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

For Mucopolysaccharidosis type 2 (Orphanet):

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

Similar variants

IDS p.Ser71Arg Likely pathogenic ★★ same residue
IDS p.Ser71Asn Pathogenic/Likely pathogenic ★★ same residue
IDS p.Ser71= Likely benign ★ same residue
IDS p.Ser71fs Pathogenic ★ same residue
IDS p.Ser71Cys 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-ser71ile (accessed [today's date]).

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