CARD8 p.Phe453=
c.1359T>C · rs188716648 · VCV1552562
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0217%, amr)
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 -0.31 | GERP -0.078, phastCons 0.029 |
| Overall | ||
| CADD | 4.974 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0217%
Admixed American · 13/59,992 alleles
Filtering AF
0.0127%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0101%
Overall
0.00235%
38/1,613,930 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0217% | 4,615 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,835 |
| European (non-Finnish) | 0.00186% | 53,631 |
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.Phe453=
- Coding
- c.1359T>C
- MANE Select
- NM_001184900
- dbSNP
- rs188716648
- Type
- single nucleotide variant
- Location
- chr19:48211965 (GRCh38)
- Gene constraint
- LOEUF 0.883 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.42 · 5 PDB
- Residue 453
- the card domain; an α-helix
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-phe453 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown