CASP8 p.Arg185=
c.553A>C · rs140527175 · VCV3033493
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.43%, afr)
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 0.23 | GERP -2.5 |
| Overall | ||
| CADD | 2.67 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.43%
African / African-American · 323/75,052 alleles
Filtering AF
0.392%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.377%
Overall
0.0232%
375/1,614,148 alleles · rare
exomes 169/1,461,822 · genomes 206/152,326 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.43% | 232 |
| Admixed American | 0.0383% | 2,610 |
| Remaining individualsnot grpmax-eligible | 0.0208% | 4,808 |
| Middle Eastern | 0.0165% | 6,062 |
| South Asian | 0.00329% | 30,362 |
| European (non-Finnish) | 0.00102% | 98,331 |
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
- CASP8
- Protein
- p.Arg185=
- Coding
- c.553A>C
- MANE Select
- NM_001372051
- dbSNP
- rs140527175
- Type
- single nucleotide variant
- Location
- chr2:201272900 (GRCh38)
- Gene constraint
- LOEUF 0.695 · pLI 0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.37 · 36 PDB
Similar variants
- CASP8 p.Arg248Trp Pathogenic/Likely pathogenic ★★ same type
- CASP8 c.306-1926A>G Uncertain significance ★★ same type
- CASP8 c.306-1935G>A Uncertain significance ★★ same type
- CASP8 c.306-1971A>G Uncertain significance ★★ same type
- CASP8 c.660+6C>T Uncertain significance ★★ same type
- CASP8 c.*107C>T Uncertain significance ★★ same type
- CASP8 p.Ala96Ser Uncertain significance ★★ ⚠ same type
- CASP8 p.Arg233Trp 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/casp8-p-arg185 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown