CARD8 p.His87Pro
c.260A>C · rs114230554 · VCV1165289
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.51%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.116 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.3 | GERP 0.49 |
| Regional constraint | o/e 0.86 | unconstrained · MANE · 29 kb · p 0.00022 · regional, not allelic |
| Overall | ||
| CADD | 1.424 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.51%
African / African-American · 1,136/74,986 alleles
Filtering AF
1.44%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.41%
Overall
0.0796%
1,285/1,613,878 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.51% | 66 |
| Remaining individualsnot grpmax-eligible | 0.12% | 833 |
| Middle Eastern | 0.0825% | 1,212 |
| Admixed American | 0.075% | 1,333 |
| South Asian | 0.00769% | 13,009 |
| European (non-Finnish) | 0.00144% | 69,406 |
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.His87Pro
- Coding
- c.260A>C
- MANE Select
- NM_001184900
- dbSNP
- rs114230554
- Type
- single nucleotide variant
- Location
- chr19:48234493 (GRCh38)
- Gene constraint
- LOEUF 0.883 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.42 · 5 PDB
- Residue 87
- 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-his87pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown