CHD4 p.Ser1364=
c.4092C>A · rs974734141 · VCV3029223
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.6e-05%, nfe)
Conditions
1
CHD4-related disorder
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 4.6 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 19.74 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.6e-05%
European (non-Finnish) · 1/1,163,270 alleles
Overall
6.33e-05%
1/1,580,310 alleles · very rare
exomes 0/1,428,492 · genomes 1/151,818 · joint denominator
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.Ser1364=
- Coding
- c.4092C>A
- MANE Select
- NM_001273
- dbSNP
- rs974734141
- Type
- single nucleotide variant
- Location
- chr12:6583082 (GRCh38)
- Gene constraint
- LOEUF 0.192 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 65.41 · 12 PDB
- Residue 1364
- the 'disordered' region
Disease context
CHD4-related disorder
Similar variants
- CHD4 p.Ser1364Tyr Uncertain significance ★ ⚠ same residue
- CHD4 p.Glu536Val Uncertain significance ★★ ⚠ same condition
- CHD4 p.Thr709Ala Uncertain significance ★★ ⚠ same condition
- CHD4 p.Arg1068Ser Likely pathogenic ★ same condition
- CHD4 p.Arg877Gln Likely pathogenic ★ same condition
- CHD4 p.Cys376Ter Likely pathogenic ★ same condition
- CHD4 p.Met1210Thr Likely pathogenic ★ ⚠ same condition
- CHD4 p.Ala1601Ser Conflicting classifications of pathogenicity ★ ⚠ 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-ser1364 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown