CHD8 p.Asp1707=
c.5121T>C · rs61729945 · VCV588114
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.42%, afr)
Conditions
1
Inborn genetic diseases
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 2.7 | GERP 2.2, phastCons 1 |
| Overall | ||
| CADD | 9.135 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.42%
African / African-American · 1,056/74,584 alleles
Filtering AF
1.34%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.32%
Overall
0.0766%
1,224/1,597,418 alleles · low-frequency
exomes 599/1,445,100 · genomes 625/152,318 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.42% | 71 |
| Remaining individualsnot grpmax-eligible | 0.134% | 746 |
| Admixed American | 0.103% | 975 |
| Middle Eastern | 0.0664% | 1,507 |
| South Asian | 0.00665% | 15,042 |
| European (non-Finnish) | 0.0012% | 83,291 |
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
- CHD8
- Protein
- p.Asp1707=
- Coding
- c.5121T>C
- MANE Select
- NM_001170629
- dbSNP
- rs61729945
- Type
- single nucleotide variant
- Location
- chr14:21395823 (GRCh38)
- Gene constraint
- LOEUF 0.154 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 55.17 · 2 PDB
- Residue 1707
- the 'disordered' region
Similar variants
- CHD8 p.Asp1707Asn Uncertain significance ★ ⚠ same residue
- CHD8 c.3882+1G>A Pathogenic/Likely pathogenic ★★ same condition
- CHD8 p.Arg1462Ter Pathogenic ★★ same condition
- CHD8 p.Arg1582Ter Pathogenic/Likely pathogenic ★★ same condition
- CHD8 p.Arg2217Ter Pathogenic ★★ same condition
- CHD8 p.Arg243Ter Pathogenic ★★ same condition
- CHD8 c.4921+4C>T Uncertain significance ★★ same condition
- CHD8 c.-1G>A Uncertain significance ★★ 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/chd8-p-asp1707 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown