CHD8 p.Pro2017=
c.6051C>T · rs372539313 · VCV2415074
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0195%, nfe)
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 2.3, phastCons 1 |
| Overall | ||
| CADD | 8.586 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0195%
European (non-Finnish) · 230/1,179,846 alleles
Filtering AF
0.0174%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0166%
Overall
0.0152%
245/1,613,752 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0195% | 5,130 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,940 |
| African / African-American | 0.00534% | 18,730 |
| Admixed American | 0.00334% | 29,984 |
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.Pro2017=
- Coding
- c.6051C>T
- MANE Select
- NM_001170629
- dbSNP
- rs372539313
- Type
- single nucleotide variant
- Location
- chr14:21393744 (GRCh38)
- Gene constraint
- LOEUF 0.154 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 55.17 · 2 PDB
- Residue 2017
- the 'interaction with fam124b' region; the 'disordered' region
Similar variants
- CHD8 p.Pro2017Leu Uncertain significance ★ ⚠ same residue
- CHD8 c.3882+1G>A Pathogenic/Likely pathogenic ★★ same type
- CHD8 p.Arg1188Ter Pathogenic ★★ same type
- CHD8 p.Arg1242Gln Likely pathogenic ★★ same type
- CHD8 p.Arg1242Ter Pathogenic ★★ same type
- CHD8 p.Arg1245Ter Pathogenic ★★ same type
- CHD8 p.Arg1337Ter Pathogenic ★★ same type
- CHD8 p.Arg1402Ter 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/chd8-p-pro2017 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown