CHD4 p.Trp1443Ter
c.4328G>A · VCV3391255
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | predicted | premature termination codon in exon 29 of 40 |
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Pangolin | Δ0.28 | loss · gain 0.19 · SpliceAI below 0.2 · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 42.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- CHD4
- Protein
- p.Trp1443Ter
- Coding
- c.4328G>A
- MANE Select
- NM_001273
- Type
- single nucleotide variant
- Location
- chr12:6582657 (GRCh38)
- Gene constraint
- LOEUF 0.192 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 65.41 · 12 PDB
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-trp1443ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown