CARD8 p.Val268Phe
c.802G>T · VCV3610212
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00568%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.21 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.43 | acceptor gain · deltas |
| Pangolin | Δ0.23 | gain · loss 0.11 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.42 | GERP 0.39, phastCons 0.031 |
| Regional constraint | o/e 0.86 | unconstrained · MANE · 29 kb · p 0.00022 · regional, not allelic |
| Overall | ||
| CADD | 22.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00568%
European (non-Finnish) · 67/1,179,962 alleles
Filtering AF
0.00454%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00417%
Overall
0.00421%
68/1,613,880 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00568% | 17,611 |
| African / African-American | 0.00133% | 74,910 |
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.Val268Phe
- Coding
- c.802G>T
- MANE Select
- NM_001184900
- Type
- single nucleotide variant
- Location
- chr19:48230671 (GRCh38)
- Gene constraint
- LOEUF 0.883 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.42 · 5 PDB
- Residue 268
- a UniProt-annotated variant site (in ibd30); the fiind domain; the 'zu5' region; a β-strand
Similar variants
- CARD8 p.Val268Ile Uncertain significance ★★ 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-val268phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown