Is IDS p.Ala387Ser (c.1159G>T) pathogenic?

IDS p.Ala387Ser (c.1159G>T) is classified Uncertain significance in IDS (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-17). AlphaMissense: likely benign (0.0671); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with IDS p.Ala387Ser (c.1159G>T)?

IDS p.Ala387Ser (c.1159G>T) is associated with Inborn genetic diseases (ClinVar).

How common is IDS p.Ala387Ser (c.1159G>T) in the general population?

IDS p.Ala387Ser (c.1159G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IDS p.Ala387Ser (c.1159G>T)?

AlphaMissense predicts likely benign (score 0.0671) — an in-silico prediction, not a clinical call.

IDS p.Ala387Ser

c.1159G>T · VCV4840106

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0671 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0671	likely benign
REVEL	0.389	indeterminate
SaProt	LLR -3.33	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.41 · evaluated, not missing
Constraint at this position
Conservation	phyloP -9.8	GERP -3.5
Regional constraint	o/e 0.78	unconstrained · MANE · 21 kb · p 5.6e-05 · regional, not allelic
Overall
CADD	0.008	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.Ala387Ser
Coding: c.1159G>T
MANE Select: NM_000202
Type: single nucleotide variant
Location: chrX:149486946 (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.Ala387Thr Benign/Likely benign ★★ 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
IDS p.Arg101His 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-ala387ser (accessed [today's date]).

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