Is IDS p.Arg313Cys (c.937C>T) pathogenic?

IDS p.Arg313Cys (c.937C>T) is classified Benign/Likely benign in IDS (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-05-01). AlphaMissense: likely benign (0.0786); Rare (popmax 0.138%, mid); Associated with mucopolysaccharidosis type 2.

What condition is associated with IDS p.Arg313Cys (c.937C>T)?

IDS p.Arg313Cys (c.937C>T) is associated with mucopolysaccharidosis type 2, mucopolysaccharidosis type 3A (ClinVar).

How common is IDS p.Arg313Cys (c.937C>T) in the general population?

IDS p.Arg313Cys (c.937C>T) is rare (popmax 0.138%, mid) (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.Arg313Cys (c.937C>T)?

AlphaMissense predicts likely benign (score 0.0786) — an in-silico prediction, not a clinical call.

IDS p.Arg313Cys

c.937C>T · rs201048643 · VCV771625

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0786 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.138%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

mucopolysaccharidosis type 2

Computational evidence

Protein change
AlphaMissense	0.0786	likely benign
REVEL	0.604	indeterminate
SaProt	LLR -12.54	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 1.6, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 21 kb · p 5.6e-05 · regional, not allelic
Overall
CADD	23.4	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 0.138% Middle Eastern · 6/4,348 alleles

Filtering AF 0.06% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.041%

Overall 0.00687% 83/1,208,143 alleles · rare exomes 74/1,096,399 · genomes 9/111,744 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.138%	725
South Asian	0.0352%	2,840
Remaining individualsnot grpmax-eligible	0.0105%	9,508
European (non-Finnish)	0.00548%	18,236
Admixed American	0.00437%	22,887
African / African-American	0.00175%	57,111

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.Arg313Cys
Coding: c.937C>T
MANE Select: NM_000202
dbSNP: rs201048643
Type: single nucleotide variant
Location: chrX:149490383 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB
Residue 313: a UniProt-annotated variant site (in mps2; uncertain significance); an α-helix

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.Arg313Ser Uncertain significance ⚠ same residue
IDS p.Arg313fs Pathogenic ★ same residue
IDS p.Arg313His 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
IDS c.1007-2A>C 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-arg313cys (accessed [today's date]).

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