Is CHD2 p.Glu977Gly (c.2930A>G) pathogenic?

CHD2 p.Glu977Gly (c.2930A>G) is classified Uncertain significance in CHD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-09). AlphaMissense: ambiguous (0.3692); Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy 94.

What condition is associated with CHD2 p.Glu977Gly (c.2930A>G)?

CHD2 p.Glu977Gly (c.2930A>G) is associated with developmental and epileptic encephalopathy 94 (ClinVar).

How common is CHD2 p.Glu977Gly (c.2930A>G) in the general population?

CHD2 p.Glu977Gly (c.2930A>G) is absent from gnomAD v4.1 (gnomAD).

How is Lennox-Gastaut syndrome inherited?

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

What do computational predictors say about CHD2 p.Glu977Gly (c.2930A>G)?

AlphaMissense predicts ambiguous (score 0.3692) — an in-silico prediction, not a clinical call.

CHD2 p.Glu977Gly

c.2930A>G · VCV3636682

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3692 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

developmental and epileptic encephalopathy 94

Computational evidence

Protein change
AlphaMissense	0.3692	ambiguous
REVEL	0.731	pathogenic-leaning
SaProt	LLR -12.42	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.3	GERP 2.6, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 6,370 bp · p 7.8e-14 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHD2
Protein: p.Glu977Gly
Coding: c.2930A>G
Type: single nucleotide variant
Location: chr15:92980868 (GRCh38)

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)

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-glu977gly (accessed [today's date]).

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