Is CHD2 p.Arg1313Pro (c.3938G>C) pathogenic?

CHD2 p.Arg1313Pro (c.3938G>C) is classified Pathogenic in CHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-18). AlphaMissense: likely pathogenic (0.9991); Very rare (popmax 8.47e-05%, nfe); Associated with developmental and epileptic encephalopathy 94.

What condition is associated with CHD2 p.Arg1313Pro (c.3938G>C)?

CHD2 p.Arg1313Pro (c.3938G>C) is associated with developmental and epileptic encephalopathy 94 (ClinVar).

How common is CHD2 p.Arg1313Pro (c.3938G>C) in the general population?

CHD2 p.Arg1313Pro (c.3938G>C) is very rare (popmax 8.47e-05%, nfe) (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.Arg1313Pro (c.3938G>C)?

AlphaMissense predicts likely pathogenic (score 0.9991) — an in-silico prediction, not a clinical call.

CHD2 p.Arg1313Pro

c.3938G>C · rs1131692012 · VCV944804

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9991 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy 94

Computational evidence

Protein change
AlphaMissense	0.9991	likely pathogenic ✓ concordant with ClinVar · top 3% in CHD2
REVEL	0.858	moderately pathogenic-leaning
SaProt	LLR -16.92	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.9, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 5,656 bp · p 4.7e-09 · regional, not allelic
Overall
CADD	26.0	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 8.47e-05% European (non-Finnish) · 1/1,179,974 alleles

Overall 6.84e-05% 1/1,461,624 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.Arg1313Pro
Coding: c.3938G>C
MANE Select: NM_001271
dbSNP: rs1131692012
Type: single nucleotide variant
Location: chr15:92998551 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81
Residue 1313: 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.Arg1313Gly Pathogenic ★★ same residue
CHD2 p.Arg1313Ter Pathogenic ★★ same residue
CHD2 p.Arg1313Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
CHD2 p.Arg1313Leu Uncertain significance ★ ⚠ same residue
CHD2 p.Arg1313= Likely benign ★ 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

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-arg1313pro (accessed [today's date]).

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