Is CHD2 p.Ser1407Ile (c.4219_4220delinsAT) pathogenic?

CHD2 p.Ser1407Ile (c.42194220delinsAT) is classified Uncertain significance in CHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-02). Absent from gnomAD; Associated with developmental and epileptic encephalopathy 94.

What condition is associated with CHD2 p.Ser1407Ile (c.4219_4220delinsAT)?

CHD2 p.Ser1407Ile (c.4219_4220delinsAT) is associated with developmental and epileptic encephalopathy 94 (ClinVar).

How common is CHD2 p.Ser1407Ile (c.4219_4220delinsAT) in the general population?

CHD2 p.Ser1407Ile (c.4219_4220delinsAT) 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.Ser1407Ile

c.4219_4220delinsAT · rs1567159959 · VCV571896

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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 7.8	GERP 1.1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 6,067 bp · p 0.73 · regional, not allelic
Region caveats
Repeat context	tandem	A-rich low complexity · ambiguous alignment · confidence, not pathogenicity

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.Ser1407Ile
Coding: c.4219_4220delinsAT
MANE Select: NM_001271
dbSNP: rs1567159959
Type: Indel
Location: chr15:93002258 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81
Residue 1407: 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.Ser1407Thr Benign/Likely benign ★★ ⚠ same residue
CHD2 p.Ser1407Tyr Uncertain significance ★ ⚠ same residue
CHD2 p.Glu412Thr Uncertain significance ★★ same condition
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.Leu461delinsGlnValTer 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-ser1407ile (accessed [today's date]).

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