CHD2 p.Ser1180=
c.3540C>T · rs76621355 · VCV238880
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.59%, afr)
Conditions
2
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 1.1 | GERP 0.89, phastCons 1 |
| Overall | ||
| CADD | 9.668 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.59%
African / African-American · 1,940/75,046 alleles
Filtering AF
2.49%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.45%
Overall
0.187%
3,026/1,614,084 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.59% | 39 |
| East Asian | 1.54% | 65 |
| Remaining individualsnot grpmax-eligible | 0.278% | 359 |
| Admixed American | 0.177% | 566 |
| Middle Eastern | 0.133% | 750 |
| South Asian | 0.0725% | 1,380 |
| European (non-Finnish) | 0.00331% | 30,257 |
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
- CHD2
- Protein
- p.Ser1180=
- Coding
- c.3540C>T
- MANE Select
- NM_001271
- dbSNP
- rs76621355
- Type
- single nucleotide variant
- Location
- chr15:92992943 (GRCh38)
- Gene constraint
- LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 60.81
- Residue 1180
- a UniProt-annotated variant site (in dee94); a UniProt-annotated variant site (found in a patient with progressive myoclonus epilepsy; uncertain significance)
Similar variants
- CHD2 p.Ser1180Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
- CHD2 c.1153+1G>C Pathogenic ★★ same condition
- CHD2 c.1809+1G>A Pathogenic/Likely pathogenic ★★ same condition
- CHD2 c.294+1G>T Likely pathogenic ★★ same condition
- CHD2 c.443+1G>A Pathogenic/Likely pathogenic ★★ same condition
- CHD2 c.693-1G>A Likely pathogenic ★★ same condition
- CHD2 p.Ala879Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
- CHD2 p.Arg1072Ter Pathogenic ★★ 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/chd2-p-ser1180 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown