Is IDS p.Gly343Arg (c.1027G>A) pathogenic?

IDS p.Gly343Arg (c.1027G>A) is classified Likely pathogenic in IDS (ClinVar, Single submitter, 1 submitter; last evaluated 2015-12-10). AlphaMissense: likely benign (0.2946); Absent from gnomAD v4.1.

How common is IDS p.Gly343Arg (c.1027G>A) in the general population?

IDS p.Gly343Arg (c.1027G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IDS p.Gly343Arg (c.1027G>A)?

AlphaMissense predicts likely benign (score 0.2946) — an in-silico prediction, not a clinical call.

IDS p.Gly343Arg

c.1027G>A · rs1557338153 · VCV432040

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2946 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2946	likely benign ⚠ discordant with ClinVar
REVEL	0.922	moderately pathogenic-leaning
SaProt	LLR -9.16	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	Δ0.35	acceptor loss · deltas
Pangolin	Δ0.21	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 21 kb · p 5.6e-05 · regional, not allelic
Overall
CADD	25.7	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.Gly343Arg
Coding: c.1027G>A
MANE Select: NM_000202
dbSNP: rs1557338153
Type: single nucleotide variant
Location: chrX:149487078 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB
Residue 343: an α-helix

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

Similar variants

IDS p.Gly343Val Likely 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
IDS c.103+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-gly343arg (accessed [today's date]).

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