CHD8 p.Arg2056=
c.6168G>A · rs780524988 · VCV3015784
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0472%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.77 · evaluated, not missing |
|---|---|---|
| Pangolin | Δ0.21 | gain · loss 0.00 · SpliceAI below 0.2 · independent |
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP -0.68, phastCons 1 |
| Overall | ||
| CADD | 11.61 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0472%
South Asian · 43/91,074 alleles
Filtering AF
0.036%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0321%
Overall
0.00285%
46/1,613,816 alleles · ultra-rare
exomes 44/1,461,674 · genomes 2/152,142 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0472% | 2,118 |
| European (non-Finnish) | 0.000254% | 393,297 |
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.Arg2056=
- Coding
- c.6168G>A
- MANE Select
- NM_001170629
- dbSNP
- rs780524988
- Type
- single nucleotide variant
- Location
- chr14:21393627 (GRCh38)
- Gene constraint
- LOEUF 0.154 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 55.17 · 2 PDB
- Residue 2056
- the 'interaction with fam124b' region; the 'disordered' region
Similar variants
- CHD8 p.Arg2056Gln Likely benign ★★ same residue
- CHD8 p.Arg2056Pro Uncertain significance ★ ⚠ same residue
- CHD8 p.Arg2056Trp Likely benign ★ 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
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-arg2056 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown