Is CHD2 p.Glu412Thr (c.1234_1235delinsAC) pathogenic?

CHD2 p.Glu412Thr (c.12341235delinsAC) is classified Uncertain significance in CHD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-17). Absent from gnomAD; Associated with developmental and epileptic encephalopathy 94.

What condition is associated with CHD2 p.Glu412Thr (c.1234_1235delinsAC)?

CHD2 p.Glu412Thr (c.1234_1235delinsAC) is associated with developmental and epileptic encephalopathy 94 (ClinVar).

How common is CHD2 p.Glu412Thr (c.1234_1235delinsAC) in the general population?

CHD2 p.Glu412Thr (c.1234_1235delinsAC) is absent from gnomAD (gnomAD).

How is Lennox-Gastaut syndrome inherited?

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

CHD2 p.Glu412Thr

c.1234_1235delinsAC · rs2053463440 · VCV1019442

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

developmental and epileptic encephalopathy 94

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 9,299 bp · p 6.4e-08 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CHD2
Protein: p.Glu412Thr
Coding: c.1234_1235delinsAC
MANE Select: NM_001271
dbSNP: rs2053463440
Type: Indel
Location: chr15:92946073 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81
Residue 412: the chromo 2 domain; a UniProt-annotated variant site (in dee94); a UniProt-annotated variant site (found in a patient with progressive myoclonus epilepsy; uncertain significance)

Full CHD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy 94 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Lennox-Gastaut syndrome (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial, Not applicable
Onset: Childhood, Infancy
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

CHD2 p.Glu412Lys Uncertain significance ★ ⚠ same residue
CHD2 c.4138-19_4138-18delinsTA Likely benign ★★ same condition
CHD2 c.1720-155_1727delinsT Likely pathogenic ★ same condition
CHD2 p.Ala869Phe Likely pathogenic ★ same condition
CHD2 p.Ala929_Val934delinsTer Pathogenic ★ same condition
CHD2 p.Glu412Ter Pathogenic ★ same residue
CHD2 p.Leu461delinsGlnValTer Pathogenic ★ same condition
CHD2 p.Pro155fs Pathogenic ★ 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/chd2-p-glu412thr (accessed [today's date]).

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