CASP12 c.680T>C
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0315%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.009 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.17 | GERP -1.4 |
| Non-coding constraint | Z 0.92 | 1 kb window · o/e 0.90 · regional · uncalibrated |
| Overall | ||
| CADD | 0.17 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0315%
African / African-American · 23/72,910 alleles
Filtering AF
0.0215%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0183%
Overall
0.00281%
43/1,532,912 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0315% | 3,170 |
| Middle Eastern | 0.0167% | 5,988 |
| Remaining individualsnot grpmax-eligible | 0.0167% | 5,989 |
| Admixed American | 0.00589% | 16,973 |
| South Asian | 0.00238% | 41,994 |
| European (non-Finnish) | 0.00035% | 286,085 |
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
- CASP12
- Coding
- c.680T>C
- Type
- single nucleotide variant
- Location
- chr11:104890511 (GRCh38)
- Structure
- AlphaFold pLDDT 77.13
Similar variants
- CASP12 p.Arg125Ter Likely benign ★★ same type
- CASP12 c.1013T>G Uncertain significance ★ same type
- CASP12 c.107T>C Uncertain significance ★ same type
- CASP12 c.19T>A Uncertain significance ★ same type
- CASP12 c.22A>G Uncertain significance ★ same type
- CASP12 c.254G>A Uncertain significance ★ same type
- CASP12 c.269G>C Uncertain significance ★ same type
- CASP12 c.274G>A 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/casp12-c-680t-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown