CARD8 p.Pro18=
c.54G>A · rs777865064 · VCV2963425
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0117%, nfe)
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 -0.5 | GERP -0.54 |
| Overall | ||
| CADD | 6.171 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0117%
European (non-Finnish) · 134/1,146,636 alleles
Filtering AF
0.0101%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00945%
Overall
0.00886%
136/1,535,824 alleles · ultra-rare
exomes 132/1,383,660 · genomes 4/152,164 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0117% | 8,557 |
| African / African-American | 0.00137% | 73,022 |
| South Asian | 0.00119% | 84,056 |
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.Pro18=
- Coding
- c.54G>A
- MANE Select
- NM_001184900
- dbSNP
- rs777865064
- Type
- single nucleotide variant
- Location
- chr19:48240967 (GRCh38)
- Gene constraint
- LOEUF 0.883 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.42 · 5 PDB
- Residue 18
- a UniProt-annotated variant site (in ibd30); the 'disordered' region
Similar variants
- CARD8 p.Pro18Leu Likely benign ★ same residue
- 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
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-pro18 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown