CHD2 p.Lys1428=
c.4284A>G · rs35339954 · VCV238883
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
rare (popmax 0.932%, afr)
Conditions
2
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 6.1 | GERP 1.5, phastCons 1 |
| Overall | ||
| CADD | 9.447 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.932%
African / African-American · 699/74,994 alleles
Filtering AF
0.875%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.852%
Overall
0.0467%
752/1,611,420 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.932% | 107 |
| Remaining individualsnot grpmax-eligible | 0.0433% | 2,311 |
| Admixed American | 0.0418% | 2,391 |
| European (non-Finnish) | 8.49e-05% | 1,178,378 |
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.Lys1428=
- Coding
- c.4284A>G
- MANE Select
- NM_001271
- dbSNP
- rs35339954
- Type
- single nucleotide variant
- Location
- chr15:93004622 (GRCh38)
- Gene constraint
- LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 60.81
- Residue 1428
- a UniProt-annotated variant site (in dee94); a UniProt-annotated variant site (found in a patient with progressive myoclonus epilepsy; uncertain significance); the 'disordered' region
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-lys1428 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown