CARD8 p.Leu82=
c.246T>C · rs2288876 · VCV1168812
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 40.9%, amr) — too common for a highly-penetrant pathogenic allele
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 -0.8 | GERP -1 |
| Overall | ||
| CADD | 0.556 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
40.9%
Admixed American · 24,520/59,944 alleles
Filtering AF
40.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 40.3%
Overall
31.8%
513,131/1,613,032 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 40.9% | 2 |
| European (non-Finnish) | 32.6% | 3 |
| South Asian | 32.6% | 3 |
| Ashkenazi Jewishnot grpmax-eligible | 32.4% | 3 |
| Remaining individualsnot grpmax-eligible | 31.1% | 3 |
| Middle Eastern | 26.1% | 4 |
| Finnishnot grpmax-eligible | 25.7% | 4 |
| East Asian | 24.4% | 4 |
| Amishnot grpmax-eligible | 23.8% | 4 |
| African / African-American | 21% | 5 |
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
- CARD8
- Protein
- p.Leu82=
- Coding
- c.246T>C
- MANE Select
- NM_001184900
- dbSNP
- rs2288876
- Type
- single nucleotide variant
- Location
- chr19:48234507 (GRCh38)
- Gene constraint
- LOEUF 0.883 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.42 · 5 PDB
- Residue 82
- a UniProt-annotated variant site (in ibd30)
Similar variants
- CARD8 c.1035+5G>A Uncertain significance ★★ same type
- CARD8 p.Ala442Pro Uncertain significance ★★ same type
- CARD8 p.Ala97Val Uncertain significance ★★ same type
- CARD8 p.Arg103His Uncertain significance ★★ same type
- CARD8 p.Arg20Trp Uncertain significance ★★ same type
- CARD8 p.Arg304Gln Uncertain significance ★★ same type
- CARD8 p.Arg310Cys Uncertain significance ★★ same type
- CARD8 p.Arg353Cys 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/card8-p-leu82 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown