CHD4 p.Pro251=
c.753C>T · rs1234359517 · VCV747659
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
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 0.3 | GERP -1.6, phastCons 0.96 |
| Overall | ||
| CADD | 9.969 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/60,020 alleles
Filtering AF
0.000553%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000207%
Overall
0.000205%
3/1,461,748 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 30,010 |
| European (non-Finnish) | 8.48e-05% | 1,179,916 |
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.Pro251=
- Coding
- c.753C>T
- MANE Select
- NM_001273
- dbSNP
- rs1234359517
- Type
- single nucleotide variant
- Location
- chr12:6601335 (GRCh38)
- Gene constraint
- LOEUF 0.192 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 65.41 · 12 PDB
- Residue 251
- the 'disordered' region
Similar variants
- CHD4 p.Pro251His Uncertain significance ★★ ⚠ same residue
- CHD4 p.Pro251Ala Conflicting classifications of pathogenicity ★ ⚠ 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-pro251 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown