CHD8 p.Ser145=
c.435C>T · rs1480707977 · VCV1931783
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0154%, sas)
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 0.98 | GERP -5.2, phastCons 1 |
| Overall | ||
| CADD | 5.077 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0154%
South Asian · 14/90,994 alleles
Filtering AF
0.0092%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00736%
Overall
0.00113%
18/1,598,982 alleles · ultra-rare
exomes 17/1,446,824 · genomes 1/152,158 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0154% | 6,500 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,178 |
| European (non-Finnish) | 0.00017% | 589,824 |
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.Ser145=
- Coding
- c.435C>T
- MANE Select
- NM_001170629
- dbSNP
- rs1480707977
- Type
- single nucleotide variant
- Location
- chr14:21431209 (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-ser145 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown