CASP2 p.Lys254=
c.762A>G · rs143669356 · VCV774665
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.821%, sas)
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 0.33, phastCons 0.003 |
| Overall | ||
| CADD | 5.164 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.821%
South Asian · 748/91,084 alleles
Filtering AF
0.772%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.753%
Overall
0.116%
1,880/1,614,192 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.821% | 122 |
| Ashkenazi Jewishnot grpmax-eligible | 0.439% | 228 |
| Middle Eastern | 0.33% | 303 |
| Remaining individualsnot grpmax-eligible | 0.133% | 753 |
| European (non-Finnish) | 0.0732% | 1,366 |
| African / African-American | 0.024% | 4,169 |
| Admixed American | 0.0133% | 7,503 |
| Finnishnot grpmax-eligible | 0.0109% | 9,149 |
| East Asian | 0.00446% | 22,446 |
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
- CASP2
- Protein
- p.Lys254=
- Coding
- c.762A>G
- MANE Select
- NM_032982
- dbSNP
- rs143669356
- Type
- single nucleotide variant
- Location
- chr7:143299937 (GRCh38)
- Gene constraint
- LOEUF 0.936 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.95 · 17 PDB
- Residue 254
- a UniProt-annotated variant site (in mrt80; likely pathogenic); an α-helix
Similar variants
- CASP2 p.Gln331Glu Uncertain significance ★★ ⚠ same type
- CASP2 p.Ala412= Likely benign ★★ same type
- CASP2 p.Gly7= Likely benign ★★ same type
- CASP2 p.Ile387= Benign/Likely benign ★★ same type
- CASP2 p.Thr267= Benign/Likely benign ★★ same type
- CASP2 p.Tyr151= Benign ★★ same type
- CASP2 p.Val29= Benign ★★ same type
- CASP2 c.876+1G>T Pathogenic ★ 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/casp2-p-lys254 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown