Is IDH2 p.Lys243= (c.729A>G) pathogenic?

IDH2 p.Lys243= (c.729A>G) is classified Likely benign in IDH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-12-22). Absent from gnomAD v4.1; Associated with d-2-hydroxyglutaric aciduria 2.

What condition is associated with IDH2 p.Lys243= (c.729A>G)?

IDH2 p.Lys243= (c.729A>G) is associated with d-2-hydroxyglutaric aciduria 2 (ClinVar).

How common is IDH2 p.Lys243= (c.729A>G) in the general population?

IDH2 p.Lys243= (c.729A>G) is absent from gnomAD v4.1 (gnomAD).

How is D-2-hydroxyglutaric aciduria inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

IDH2 p.Lys243=

c.729A>G · rs1596073596 · VCV731923

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

d-2-hydroxyglutaric aciduria 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -0.55, phastCons 1
Overall
CADD	13.07	PHRED · no single calibrated threshold — expert panels disagree

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: IDH2
Protein: p.Lys243=
Coding: c.729A>G
MANE Select: NM_002168
dbSNP: rs1596073596
Type: single nucleotide variant
Location: chr15:90087525 (GRCh38)
Gene constraint: LOEUF 0.502 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 92.07 · 13 PDB

Full IDH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

d-2-hydroxyglutaric aciduria 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For D-2-hydroxyglutaric aciduria (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

IDH2 p.Arg140Gln Pathogenic/Likely pathogenic ★★ same condition
IDH2 c.1271+3G>A Uncertain significance ★★ same condition
IDH2 c.534+2T>C Uncertain significance ★★ same condition
IDH2 p.Ala214Thr Uncertain significance ★★ ⚠ same condition
IDH2 p.Arg362Trp Uncertain significance ★★ ⚠ same condition
IDH2 p.Arg393Lys Uncertain significance ★★ ⚠ same condition
IDH2 p.Arg60His Uncertain significance ★★ ⚠ same condition
IDH2 p.Asp439Asn 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/idh2-p-lys243 (accessed [today's date]).

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