CASP8AP2 p.Val636Phe
c.1906G>T · VCV3263456
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00456%, eas)
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 2.6 | GERP -1.5, phastCons 1 |
| Regional constraint | o/e 0.76 | unconstrained · MANE · 22 kb · p 7.8e-31 · regional, not allelic |
| Overall | ||
| CADD | 15.44 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00456%
East Asian · 1/21,946 alleles
Filtering AF
0.000648%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000243%
Overall
0.000579%
7/1,208,196 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00456% | 21,946 |
| Admixed American | 0.00391% | 25,572 |
| South Asian | 0.00115% | 86,648 |
| European (non-Finnish) | 0.000294% | 339,675 |
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
- CASP8AP2
- Protein
- p.Val636Phe
- Coding
- c.1906G>T
- MANE Select
- NM_001137667
- Type
- single nucleotide variant
- Location
- chr6:89863615 (GRCh38)
- Gene constraint
- LOEUF 0.209 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 44.28 · 4 PDB
Similar variants
- CASP8AP2 p.Val636Ile Uncertain significance ★ same residue
- CASP8AP2 p.Ala1030Ser Uncertain significance ★ same type
- CASP8AP2 p.Ala1518Asp Uncertain significance ★ same type
- CASP8AP2 p.Ala1731Thr Uncertain significance ★ same type
- CASP8AP2 p.Ala1748Asp Uncertain significance ★ same type
- CASP8AP2 p.Ala1779Gly Uncertain significance ★ same type
- CASP8AP2 p.Ala1884Val Uncertain significance ★ same type
- CASP8AP2 p.Ala19Gly 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/casp8ap2-p-val636phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown