CHD4 p.Pro1764=
c.5292T>C · rs71584868 · VCV770409
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 1.2 | GERP -3.2, phastCons 1 |
| Overall | ||
| CADD | 10.16 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Ashkenazi Jewishnot grpmax-eligible | 1.34% | 75 |
| European (non-Finnish)grpmax | 0.845% | 118 |
| Remaining individualsnot grpmax-eligible | 0.774% | 129 |
| Middle Eastern | 0.643% | 155 |
| Admixed American | 0.362% | 277 |
| Finnishnot grpmax-eligible | 0.169% | 593 |
| African / African-American | 0.163% | 615 |
| South Asian | 0.102% | 979 |
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
- CHD4
- Protein
- p.Pro1764=
- Coding
- c.5292T>C
- MANE Select
- NM_001273
- dbSNP
- rs71584868
- Type
- single nucleotide variant
- Location
- chr12:6577854 (GRCh38)
- Gene constraint
- LOEUF 0.192 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 65.41 · 12 PDB
- Residue 1764
- the 'required for interaction with pcnt' region; an α-helix
Disease context
Sifrim-Hitz-Weiss syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor CHD4-related neurodevelopmental disorder (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- Childhood, Infancy
Similar variants
- CHD4 p.Arg1068His Pathogenic/Likely pathogenic ★★ same condition
- CHD4 p.Arg1173Gln Pathogenic/Likely pathogenic ★★ same condition
- CHD4 p.Arg1173Trp Pathogenic/Likely pathogenic ★★ same condition
- CHD4 p.Arg1177Cys Pathogenic/Likely pathogenic ★★ same condition
- CHD4 p.Arg1183Cys Pathogenic/Likely pathogenic ★★ same condition
- CHD4 p.Arg1183His Pathogenic/Likely pathogenic ★★ same condition
- CHD4 p.Arg1340Cys Pathogenic ★★ same condition
- CHD4 p.Arg887Gln 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/chd4-p-pro1764 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown