CHD4 p.Cys373=
c.1119C>T · rs779177743 · VCV2642629
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, mid)
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 1.5 | GERP 0.66, phastCons 1 |
| Overall | ||
| CADD | 12.72 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,062 alleles
Filtering AF
0.00582%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00318%
Overall
0.00378%
61/1,614,030 alleles · ultra-rare
exomes 57/1,461,888 · genomes 4/152,142 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,031 |
| Admixed American | 0.005% | 20,002 |
| European (non-Finnish) | 0.00449% | 22,265 |
| Finnishnot grpmax-eligible | 0.00312% | 32,002 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,506 |
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.Cys373=
- Coding
- c.1119C>T
- MANE Select
- NM_001273
- dbSNP
- rs779177743
- Type
- single nucleotide variant
- Location
- chr12:6600340 (GRCh38)
- Gene constraint
- LOEUF 0.192 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 65.41 · 12 PDB
Similar variants
- CHD4 p.Cys373Arg Likely pathogenic ★ same residue
- CHD4 p.Cys373Gly Uncertain significance ★ ⚠ same residue
- 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
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-cys373 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown