Is IDS p.Asp56Tyr (c.166G>T) pathogenic?

IDS p.Asp56Tyr (c.166G>T) is classified Likely benign in IDS (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-01). AlphaMissense: likely benign (0.1965); Ultra-rare (popmax 0.023%, mid).

How common is IDS p.Asp56Tyr (c.166G>T) in the general population?

IDS p.Asp56Tyr (c.166G>T) is ultra-rare (popmax 0.023%, mid) (gnomAD).

What do computational predictors say about IDS p.Asp56Tyr (c.166G>T)?

AlphaMissense predicts likely benign (score 0.1965) — an in-silico prediction, not a clinical call.

IDS p.Asp56Tyr

c.166G>T · VCV4875015

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1965 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.023%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1965	likely benign
REVEL	0.69	pathogenic-leaning
SaProt	LLR -12.44	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 1.4, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 118 bp · p 0.0036 · regional, not allelic
Overall
CADD	20.5	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 0.023% Middle Eastern · 1/4,350 alleles

Overall 8.28e-05% 1/1,208,353 alleles · ultra-rare exomes 1/1,094,485 · genomes 0/113,868 · joint denominator

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.Asp56Tyr
Coding: c.166G>T
MANE Select: NM_000202
Type: single nucleotide variant
Location: chrX:149504231 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB

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

Similar variants

IDS p.Asp56Asn Uncertain significance ★ ⚠ same residue
IDS p.Asp56fs 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
IDS c.1007-2A>C Pathogenic/Likely pathogenic ★★ same type
IDS c.1007-8T>G Pathogenic/Likely 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-asp56tyr (accessed [today's date]).

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