Is CHD2 p.Pro833Ser (c.2497C>T) pathogenic?

CHD2 p.Pro833Ser (c.2497C>T) is classified Uncertain significance in CHD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-16). AlphaMissense: ambiguous (0.345); Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy 94.

What condition is associated with CHD2 p.Pro833Ser (c.2497C>T)?

CHD2 p.Pro833Ser (c.2497C>T) is associated with developmental and epileptic encephalopathy 94 (ClinVar).

How common is CHD2 p.Pro833Ser (c.2497C>T) in the general population?

CHD2 p.Pro833Ser (c.2497C>T) 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.Pro833Ser (c.2497C>T)?

AlphaMissense predicts ambiguous (score 0.345) — an in-silico prediction, not a clinical call.

CHD2 p.Pro833Ser

c.2497C>T · rs2053851835 · VCV1699637

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.345 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,594,338)

Conditions

developmental and epileptic encephalopathy 94

Computational evidence

Protein change
AlphaMissense	0.345	ambiguous
REVEL	0.364	indeterminate
SaProt	LLR -8.31	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 18 kb · p 1e-19 · regional, not allelic
Overall
CADD	25.7	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

No allele count reported in gnomAD v4.1 (AN 1,594,338). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CHD2
Protein: p.Pro833Ser
Coding: c.2497C>T
MANE Select: NM_001271
dbSNP: rs2053851835
Type: single nucleotide variant
Location: chr15:92972409 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81
Residue 833: the helicase c-terminal domain; 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 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-p-pro833ser (accessed [today's date]).

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