CHD8 p.Ile469=
c.1407T>C · rs190978463 · VCV196317
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
rare (popmax 0.193%, 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 1 | GERP -5.6, phastCons 0.99 |
| Overall | ||
| CADD | 8.248 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.193%
African / African-American · 145/75,064 alleles
Filtering AF
0.168%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.158%
Overall
0.00991%
160/1,614,036 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.193% | 518 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,681 |
| Admixed American | 0.00666% | 15,005 |
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.Ile469=
- Coding
- c.1407T>C
- MANE Select
- NM_001170629
- dbSNP
- rs190978463
- Type
- single nucleotide variant
- Location
- chr14:21428063 (GRCh38)
- Gene constraint
- LOEUF 0.154 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 55.17 · 2 PDB
- Residue 469
- the 'disordered' region
Similar variants
- CHD8 p.Ile469Thr 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-ile469 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown