CHD8 p.Arg2530=
c.7590G>A · rs371759126 · VCV1919602
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00296%, 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 4.1 | GERP 1.1, phastCons 1 |
| Overall | ||
| CADD | 10.54 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00296%
European (non-Finnish) · 34/1,146,816 alleles
Filtering AF
0.00213%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00188%
Overall
0.00239%
37/1,550,686 alleles · very rare
exomes 33/1,399,504 · genomes 4/151,182 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00296% | 33,730 |
| African / African-American | 0.00275% | 36,315 |
| Remaining individualsnot grpmax-eligible | 0.00166% | 60,108 |
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.Arg2530=
- Coding
- c.7590G>A
- MANE Select
- NM_001170629
- dbSNP
- rs371759126
- Type
- single nucleotide variant
- Location
- chr14:21385769 (GRCh38)
- Gene constraint
- LOEUF 0.154 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 55.17 · 2 PDB
- Residue 2530
- the 'disordered' region
Similar variants
- CHD8 p.Arg2530Gln Uncertain significance ★ ⚠ same residue
- CHD8 p.Arg2530Gly Uncertain significance ★ ⚠ same residue
- CHD8 p.Arg2530Leu 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
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-arg2530 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown