CACNG2 p.Ser253=
c.759C>A · rs141608078 · VCV757564
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.139%, afr)
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 1.4 | GERP -0.43, phastCons 1 |
| Overall | ||
| CADD | 8.941 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.139%
African / African-American · 104/75,062 alleles
Filtering AF
0.117%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.109%
Overall
0.00737%
119/1,614,112 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.139% | 722 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,250 |
| Admixed American | 0.00666% | 15,009 |
| South Asian | 0.0011% | 91,086 |
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
- CACNG2
- Protein
- p.Ser253=
- Coding
- c.759C>A
- MANE Select
- NM_006078
- dbSNP
- rs141608078
- Type
- single nucleotide variant
- Location
- chr22:36564564 (GRCh38)
- Gene constraint
- LOEUF 0.271 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 66.26 · 5 PDB
- Residue 253
- the 'disordered' region; a modified residue (phosphoserine)
Similar variants
- CACNG2 p.Ala100Ser Uncertain significance ★★ ⚠ same type
- CACNG2 p.Ala214Thr Uncertain significance ★★ ⚠ same type
- CACNG2 p.Arg319Pro Uncertain significance ★★ ⚠ same type
- CACNG2 p.Gln298Arg Uncertain significance ★★ ⚠ same type
- CACNG2 p.Glu126Lys Uncertain significance ★★ ⚠ same type
- CACNG2 c.212-12C>A Likely benign ★★ same type
- CACNG2 p.Val193= Likely benign ★★ same type
- CACNG2 c.436+1G>A Uncertain significance ★ 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/cacng2-p-ser253 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown