Is CHD2 c.692+5G>A pathogenic?

CHD2 c.692+5G>A is classified Uncertain significance in CHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-19). Very rare (popmax 0.0011%, sas); Associated with developmental and epileptic encephalopathy 94.

What condition is associated with CHD2 c.692+5G>A?

CHD2 c.692+5G>A is associated with developmental and epileptic encephalopathy 94 (ClinVar).

How common is CHD2 c.692+5G>A in the general population?

CHD2 c.692+5G>A is very rare (popmax 0.0011%, sas) (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.692+5G>A

rs183427060 · VCV2838975

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 +5	donor splice region (+5, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.9	GERP -1.4, phastCons 0.94
Non-coding constraint	Z 1.37	1 kb window · o/e 0.90 · regional · uncalibrated
Overall
CADD	17.21	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,998 alleles

Overall 0.000124% 2/1,612,388 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,452
South Asiangrpmax	0.0011%	90,998

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.692+5G>A
MANE Select: NM_001271
dbSNP: rs183427060
Type: single nucleotide variant
Location: chr15:92939723 (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 c.1153+1G>C Pathogenic ★★ same condition
CHD2 c.1809+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHD2 c.294+1G>T Likely pathogenic ★★ same condition
CHD2 c.443+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHD2 c.693-1G>A Likely pathogenic ★★ same condition
CHD2 p.Ala879Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
CHD2 p.Arg1072Ter Pathogenic ★★ same condition
CHD2 p.Arg1137Ter Pathogenic/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-692-plus-5g-a (accessed [today's date]).

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