Is CHD2 c.443+18del pathogenic?

CHD2 c.443+18del is classified Benign in CHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-25). Very rare (popmax 0.000171%, nfe); Associated with developmental and epileptic encephalopathy 94.

What condition is associated with CHD2 c.443+18del?

CHD2 c.443+18del is associated with developmental and epileptic encephalopathy 94 (ClinVar).

How common is CHD2 c.443+18del in the general population?

CHD2 c.443+18del is very rare (popmax 0.000171%, nfe) (gnomAD).

How is Lennox-Gastaut syndrome inherited?

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

CHD2 c.443+18del

VCV4761043

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000171%, nfe)

Conditions

developmental and epileptic encephalopathy 94

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +18	near-intronic (+18 nt from the splice site)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.036	GERP -3.9, phastCons 0.004
Non-coding constraint	Z -1.00	1 kb window · o/e 1.07 · regional · uncalibrated
Overall
CADD	17.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000171% European (non-Finnish) · 2/1,168,756 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000125% 2/1,595,376 alleles · very rare

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: CHD2
Coding: c.443+18del
MANE Select: NM_001271
Type: Deletion
Location: chr15:92929105 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81

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.Glu1412fs Pathogenic ★★ same condition
CHD2 p.Lys1393fs 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-c-443-plus-18del (accessed [today's date]).

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