Is IDS p.Ser464Thr (c.1391G>C) pathogenic?

IDS p.Ser464Thr (c.1391G>C) is classified Uncertain significance in IDS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). AlphaMissense: likely benign (0.219); Absent from gnomAD v4.1.

How common is IDS p.Ser464Thr (c.1391G>C) in the general population?

IDS p.Ser464Thr (c.1391G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IDS p.Ser464Thr (c.1391G>C)?

AlphaMissense predicts likely benign (score 0.219) — an in-silico prediction, not a clinical call.

IDS p.Ser464Thr

c.1391G>C · VCV4535580

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.219 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.219	likely benign
REVEL	0.78	moderately pathogenic-leaning
SaProt	LLR -9.24	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 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 21 kb · p 5.6e-05 · regional, not allelic
Overall
CADD	23.3	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.Ser464Thr
Coding: c.1391G>C
MANE Select: NM_000202
Type: single nucleotide variant
Location: chrX:149483008 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB
Residue 464: a β-strand

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

Similar variants

IDS p.Ser464Arg Likely pathogenic ★ same residue
IDS p.Ser464Gly Uncertain significance ★ ⚠ same residue
IDS p.Ser464_Tyr466del Likely pathogenic ★ same residue
IDS p.Ser464fs Pathogenic ★ same residue
IDS c.1006+1G>C Pathogenic ★★ same type
IDS c.1006+1G>T Pathogenic ★★ same type
IDS c.1007-133A>G Likely pathogenic ★★ same type
IDS c.1007-1G>A Pathogenic ★★ same type

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-ser464thr (accessed [today's date]).

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