CARD8 p.Ala346Val
c.1037C>T · rs1205153080 · VCV1934511
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00448%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.03 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.025 | GERP -3 |
| Regional constraint | o/e 0.86 | unconstrained · MANE · 29 kb · p 0.00022 · regional, not allelic |
| Overall | ||
| CADD | 9.68 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00448%
East Asian · 2/44,594 alleles
Filtering AF
0.000743%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000479%
Overall
0.0012%
19/1,589,798 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00448% | 22,297 |
| Remaining individualsnot grpmax-eligible | 0.00327% | 30,618 |
| African / African-American | 0.00135% | 74,294 |
| South Asian | 0.00114% | 87,928 |
| European (non-Finnish) | 0.00112% | 89,676 |
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.Ala346Val
- Coding
- c.1037C>T
- MANE Select
- NM_001184900
- dbSNP
- rs1205153080
- Type
- single nucleotide variant
- Location
- chr19:48221854 (GRCh38)
- Gene constraint
- LOEUF 0.883 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.42 · 5 PDB
- Residue 346
- a UniProt-annotated variant site (in ibd30); the fiind domain; the 'upa' region
Similar variants
- CARD8 p.Ala346= 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-ala346val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown