CHD2 p.Glu578=
c.1734A>G · rs762612275 · VCV589802
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00464%, sas)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.52 | GERP -2.8, phastCons 0.86 |
| Overall | ||
| CADD | 7.028 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00464%
South Asian · 4/86,254 alleles
Filtering AF
0.00158%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00093%
Overall
0.000756%
12/1,587,972 alleles · very rare
exomes 12/1,435,624 · genomes 0/152,348 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00464% | 21,563 |
| European (non-Finnish) | 0.000684% | 146,209 |
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.Glu578=
- Coding
- c.1734A>G
- MANE Select
- NM_001271
- dbSNP
- rs762612275
- Type
- single nucleotide variant
- Location
- chr15:92955437 (GRCh38)
- Gene constraint
- LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 60.81
- Residue 578
- the helicase atp-binding domain; a UniProt-annotated variant site (in dee94); a UniProt-annotated variant site (found in a patient with progressive myoclonus epilepsy; uncertain significance)
Similar variants
- CHD2 c.443+1G>A Pathogenic/Likely pathogenic ★★ same condition
- CHD2 p.Ala879Val Pathogenic/Likely pathogenic ★★ same condition
- CHD2 p.Arg1152Trp Pathogenic/Likely pathogenic ★★ same condition
- CHD2 p.Arg1637Ter Pathogenic ★★ same condition
- CHD2 p.Arg1679Ter Pathogenic ★★ same condition
- CHD2 p.Arg699Trp Pathogenic/Likely pathogenic ★★ same condition
- CHD2 p.Arg804Ter Pathogenic ★★ same condition
- CHD2 p.Thr645Met 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-glu578 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown