Is CHD2 p.Lys1393fs (c.4176_4177del) pathogenic?

CHD2 p.Lys1393fs (c.41764177del) is classified Pathogenic in CHD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-02). Absent from gnomAD; Associated with developmental and epileptic encephalopathy 94.

What condition is associated with CHD2 p.Lys1393fs (c.4176_4177del)?

CHD2 p.Lys1393fs (c.4176_4177del) is associated with developmental and epileptic encephalopathy 94 (ClinVar).

How common is CHD2 p.Lys1393fs (c.4176_4177del) in the general population?

CHD2 p.Lys1393fs (c.4176_4177del) 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.Lys1393fs

c.4176_4177del · rs2141873663 · VCV1219194

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

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.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 33 of 39
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.1, phastCons 1
Region caveats
Repeat context	tandem	A-rich low complexity · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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.Lys1393fs
Coding: c.4176_4177del
MANE Select: NM_001271
dbSNP: rs2141873663
Type: Deletion
Location: chr15:93002214 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81
Residue 1393: a UniProt-annotated variant site (in dee94); a UniProt-annotated variant site (found in a patient with progressive myoclonus epilepsy; uncertain significance); the 'disordered' region

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.Lys1393Asn Uncertain significance ★ ⚠ same residue
CHD2 p.Glu1412fs Pathogenic ★★ same condition
CHD2 p.Lys174_Val175insTer Pathogenic/Likely pathogenic ★★ same condition
CHD2 p.Pro399fs Pathogenic ★★ same condition
CHD2 c.1199-12del Benign/Likely benign ★★ same condition
CHD2 c.381+12del Likely benign ★★ same condition
CHD2 p.Lys1411del Benign/Likely benign ★★ same condition
CHD2 c.1151_1153+4del Likely 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-lys1393fs (accessed [today's date]).

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