CHD8 p.Gln121=
c.363A>G · rs769622502 · VCV1203443
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0189%, 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 4.9 | GERP 2, phastCons 1 |
| Overall | ||
| CADD | 13.18 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0189%
European (non-Finnish) · 221/1,171,406 alleles
Filtering AF
0.0167%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.016%
Overall
0.0147%
233/1,582,070 alleles · ultra-rare
exomes 219/1,429,888 · genomes 14/152,182 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0189% | 5,300 |
| Remaining individualsnot grpmax-eligible | 0.0178% | 5,617 |
| African / African-American | 0.00134% | 74,560 |
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.Gln121=
- Coding
- c.363A>G
- MANE Select
- NM_001170629
- dbSNP
- rs769622502
- Type
- single nucleotide variant
- Location
- chr14:21431281 (GRCh38)
- Gene constraint
- LOEUF 0.154 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 55.17 · 2 PDB
Similar variants
- 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
- CHD8 p.Arg1460Ter 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-gln121 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown