CHD4 p.Asp746=
c.2238C>T · rs141301378 · VCV736489
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.567%, sas)
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 -0.28 | GERP -1.5, phastCons 0.014 |
| Overall | ||
| CADD | 4.394 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.567%
South Asian · 516/91,084 alleles
Filtering AF
0.526%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.51%
Overall
0.089%
1,436/1,614,192 alleles · rare
exomes 1,261/1,461,864 · genomes 175/152,328 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.567% | 177 |
| Finnishnot grpmax-eligible | 0.465% | 215 |
| Remaining individualsnot grpmax-eligible | 0.064% | 1,562 |
| European (non-Finnish) | 0.0484% | 2,067 |
| Middle Eastern | 0.033% | 3,031 |
| African / African-American | 0.0107% | 9,383 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,604 |
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
- CHD4
- Protein
- p.Asp746=
- Coding
- c.2238C>T
- MANE Select
- NM_001273
- dbSNP
- rs141301378
- Type
- single nucleotide variant
- Location
- chr12:6594534 (GRCh38)
- Gene constraint
- LOEUF 0.192 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 65.41 · 12 PDB
- Residue 746
- the helicase atp-binding domain
Similar variants
- CHD4 p.Arg1068His Pathogenic/Likely pathogenic ★★ same type
- CHD4 p.Arg1173Gln Pathogenic/Likely pathogenic ★★ same type
- CHD4 p.Arg1173Trp Pathogenic/Likely pathogenic ★★ same type
- CHD4 p.Arg1177Cys Pathogenic/Likely pathogenic ★★ same type
- CHD4 p.Arg1177His Pathogenic/Likely pathogenic ★★ same type
- CHD4 p.Arg1183Cys Pathogenic/Likely pathogenic ★★ same type
- CHD4 p.Arg1183His Pathogenic/Likely pathogenic ★★ same type
- CHD4 p.Arg1340Cys Pathogenic ★★ same type
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/chd4-p-asp746 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown