CHD2 p.Arg836His
c.2507G>A · rs1429832116 · VCV976353
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9944 | likely pathogenic |
|---|---|---|
| REVEL | 0.937 | strongly pathogenic-leaning |
| SaProt | LLR -12.70 | 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 12 | GERP 2.9, phastCons 1 |
| Regional constraint | o/e 0.44 | unconstrained · MANE · 18 kb · p 1e-19 · regional, not allelic |
| Overall | ||
| CADD | 35.0 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,586 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,223 |
| South Asiangrpmax | 0.0011% | 91,086 |
| European (non-Finnish) | 0.000254% | 393,161 |
Ashkenazi Jewish 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
- Protein
- p.Arg836His
- Coding
- c.2507G>A
- MANE Select
- NM_001271
- dbSNP
- rs1429832116
- Type
- single nucleotide variant
- Location
- chr15:92974880 (GRCh38)
- Gene constraint
- LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 60.81
- Residue 836
- 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)
Disease context
developmental and epileptic encephalopathy 94 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor 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.Arg836Cys Uncertain significance ★★ ⚠ 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
- CHD2 p.Arg1072Ter 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-arg836his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown