Is IDH2 p.Arg6= (c.16C>A) pathogenic?

IDH2 p.Arg6= (c.16C>A) is classified Benign/Likely benign in IDH2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-03-01). Rare (popmax 0.47%, afr); Associated with d-2-hydroxyglutaric aciduria 2.

What condition is associated with IDH2 p.Arg6= (c.16C>A)?

IDH2 p.Arg6= (c.16C>A) is associated with d-2-hydroxyglutaric aciduria 2 (ClinVar).

How common is IDH2 p.Arg6= (c.16C>A) in the general population?

IDH2 p.Arg6= (c.16C>A) is rare (popmax 0.47%, afr) (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.Arg6=

c.16C>A · rs549177872 · VCV1601335

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.47%, afr)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.3	GERP 0.19, phastCons 1
Overall
CADD	13.68	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.47% African / African-American · 313/66,594 alleles

Filtering AF 0.427% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.41%

Overall 0.0244% 332/1,360,676 alleles · rare exomes 136/1,209,412 · genomes 196/151,264 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.47%	213
Remaining individualsnot grpmax-eligible	0.022%	4,547
Admixed American	0.0186%	5,388
European (non-Finnish)	9.56e-05%	1,046,312

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: IDH2
Protein: p.Arg6=
Coding: c.16C>A
MANE Select: NM_002168
dbSNP: rs549177872
Type: single nucleotide variant
Location: chr15:90102375 (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-arg6 (accessed [today's date]).

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