Is CHD2 p.Trp1261fs (c.3780dup) pathogenic?

CHD2 p.Trp1261fs (c.3780dup) is classified Pathogenic in CHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-15). Absent from gnomAD; Associated with developmental and epileptic encephalopathy 94.

What condition is associated with CHD2 p.Trp1261fs (c.3780dup)?

CHD2 p.Trp1261fs (c.3780dup) is associated with developmental and epileptic encephalopathy 94 (ClinVar).

How common is CHD2 p.Trp1261fs (c.3780dup) in the general population?

CHD2 p.Trp1261fs (c.3780dup) 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.Trp1261fs

c.3780dup · rs2054200651 · VCV982387

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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 30 of 39
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1

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.Trp1261fs
Coding: c.3780dup
MANE Select: NM_001271
dbSNP: rs2054200651
Type: Duplication
Location: chr15:92997297 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81
Residue 1261: 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.Trp1261Ser Pathogenic/Likely pathogenic ★★ same residue
CHD2 p.Trp1261Ter Pathogenic ★★ same residue
CHD2 p.Trp1261Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
CHD2 p.Gln1392fs Pathogenic ★★ same condition
CHD2 p.Gly1575_Lys1576insTer Pathogenic/Likely pathogenic ★★ same condition
CHD2 p.Tyr1246fs Pathogenic ★★ same condition
CHD2 c.3595+18dup Benign/Likely benign ★★ same condition
CHD2 c.4592+3_4592+5dup Likely benign ★★ 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-trp1261fs (accessed [today's date]).

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