Is CHD2 p.Arg1152Gln (c.3455G>A) pathogenic?

CHD2 p.Arg1152Gln (c.3455G>A) is classified Pathogenic in CHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-05). AlphaMissense: ambiguous (0.5308); Very rare (popmax 6.89e-05%); Associated with developmental and epileptic encephalopathy 94.

What condition is associated with CHD2 p.Arg1152Gln (c.3455G>A)?

CHD2 p.Arg1152Gln (c.3455G>A) is associated with developmental and epileptic encephalopathy 94 (ClinVar).

How common is CHD2 p.Arg1152Gln (c.3455G>A) in the general population?

CHD2 p.Arg1152Gln (c.3455G>A) is very rare (popmax 6.89e-05%) (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.Arg1152Gln (c.3455G>A)?

AlphaMissense predicts ambiguous (score 0.5308) — an in-silico prediction, not a clinical call.

CHD2 p.Arg1152Gln

c.3455G>A · rs2505576989 · VCV2058262

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5308 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.89e-05%)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

developmental and epileptic encephalopathy 94

Computational evidence

Protein change
AlphaMissense	0.5308	ambiguous
REVEL	0.765	pathogenic-leaning
SaProt	LLR -11.09	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.24 · evaluated, not missing
Pangolin	Δ0.38	loss · gain 0.01 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.23	constrained · MANE · 7,276 bp · p 4.1e-09 · regional, not allelic
Overall
CADD	35.0	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

Grpmax group 6.89e-05%

Overall 6.89e-05% 1/1,450,556 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
Protein: p.Arg1152Gln
Coding: c.3455G>A
MANE Select: NM_001271
dbSNP: rs2505576989
Type: single nucleotide variant
Location: chr15:92991517 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81
Residue 1152: 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.Arg1152Trp Pathogenic/Likely pathogenic ★★ same residue
CHD2 p.Arg1152Gly Likely pathogenic ★ same residue
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

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-arg1152gln (accessed [today's date]).

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