CHD8 p.Pro1371=
c.4113C>G · rs576454823 · VCV1329580
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0134%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.076 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.6 | GERP -1.4, phastCons 1 |
| Overall | ||
| CADD | 6.887 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0134%
African / African-American · 10/74,842 alleles
Filtering AF
0.00724%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0055%
Overall
0.00119%
19/1,601,552 alleles · ultra-rare
exomes 15/1,449,336 · genomes 4/152,216 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0134% | 7,484 |
| Remaining individualsnot grpmax-eligible | 0.0129% | 7,757 |
| Admixed American | 0.00172% | 58,052 |
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.Pro1371=
- Coding
- c.4113C>G
- MANE Select
- NM_001170629
- dbSNP
- rs576454823
- Type
- single nucleotide variant
- Location
- chr14:21401463 (GRCh38)
- Gene constraint
- LOEUF 0.154 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 55.17 · 2 PDB
Similar variants
- CHD8 p.Pro1371Leu 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-pro1371 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown