Is IDS p.Arg101His (c.302G>A) pathogenic?

IDS p.Arg101His (c.302G>A) is classified Uncertain significance in IDS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-13). AlphaMissense: likely benign (0.0698); Very rare (popmax 0.00909%, eas); Associated with Inborn genetic diseases.

What condition is associated with IDS p.Arg101His (c.302G>A)?

IDS p.Arg101His (c.302G>A) is associated with Inborn genetic diseases (ClinVar).

How common is IDS p.Arg101His (c.302G>A) in the general population?

IDS p.Arg101His (c.302G>A) is very rare (popmax 0.00909%, eas) (gnomAD).

What do computational predictors say about IDS p.Arg101His (c.302G>A)?

AlphaMissense predicts likely benign (score 0.0698) — an in-silico prediction, not a clinical call.

IDS p.Arg101His

c.302G>A · rs1391120386 · VCV2661615

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0698 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00909%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0698	likely benign
REVEL	0.719	pathogenic-leaning
SaProt	LLR -6.20	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.6	GERP -2.2, phastCons 1
Regional constraint	o/e 0.07	constrained · MANE · 819 bp · p 6.4e-10 · regional, not allelic
Overall
CADD	19.65	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 0.00909% East Asian · 3/32,988 alleles

Filtering AF 0.00241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00127%

Overall 0.000592% 7/1,182,502 alleles · very rare exomes 6/1,071,819 · genomes 1/110,683 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00909%	10,996
South Asian	0.00184%	54,350
European (non-Finnish)	0.000341%	292,902

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.Arg101His
Coding: c.302G>A
MANE Select: NM_000202
dbSNP: rs1391120386
Type: single nucleotide variant
Location: chrX:149503428 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

IDS p.Arg101Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
IDS p.Arg101Ser Uncertain significance ★ ⚠ same residue
IDS p.Arg172Ter Pathogenic ★★ same condition
IDS p.Asp269Val Pathogenic/Likely pathogenic ★★ same condition
IDS p.Pro469Arg Likely pathogenic ★★ same condition
IDS p.Ser71Arg Likely pathogenic ★★ same condition
IDS p.Tyr499Ter Pathogenic/Likely pathogenic ★★ same condition
IDS p.Ala317Asp Uncertain significance ★★ ⚠ 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-arg101his (accessed [today's date]).

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