CCAR2 p.Ala578=
c.1734G>A · rs141217161 · VCV746744
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0853%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.161 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.4 | GERP -3.8 |
| Overall | ||
| CADD | 0.624 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0853%
African / African-American · 64/74,988 alleles
Filtering AF
0.0686%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0625%
Overall
0.00669%
108/1,613,770 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0853% | 1,172 |
| Remaining individualsnot grpmax-eligible | 0.0224% | 4,464 |
| Admixed American | 0.0167% | 5,998 |
| Middle Eastern | 0.0165% | 6,058 |
| South Asian | 0.00659% | 15,180 |
| European (non-Finnish) | 0.0011% | 90,760 |
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
- CCAR2
- Protein
- p.Ala578=
- Coding
- c.1734G>A
- MANE Select
- NM_001393997
- dbSNP
- rs141217161
- Type
- single nucleotide variant
- Location
- chr8:22616137 (GRCh38)
- Gene constraint
- LOEUF 0.288 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 69.61 · 1 PDB
- Residue 578
- the 'disordered' region
Similar variants
- CCAR2 p.Ala578Thr Uncertain significance ★ ⚠ same residue
- CCAR2 p.Ala388= Benign ★★ same type
- CCAR2 p.Ala794= Benign ★★ same type
- CCAR2 p.Arg336= Likely benign ★★ same type
- CCAR2 c.1990+1G>T Uncertain significance ★ same type
- CCAR2 c.2521+1G>A Uncertain significance ★ same type
- CCAR2 c.927+38G>C Uncertain significance ★ same type
- CCAR2 p.Ala214Ser 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/ccar2-p-ala578 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown