CASP14 p.Glu59=
c.177G>A · rs112231728 · VCV713661
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.198%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.54 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.69 | loss · gain 0.27 · SpliceAI calls gain · independent |
| Constraint at this position | ||
| Conservation | phyloP 9.5 | GERP 1.4, phastCons 1 |
| Overall | ||
| CADD | 23.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.198%
European (non-Finnish) · 2,333/1,180,024 alleles
Filtering AF
0.191%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.188%
Overall
0.152%
2,461/1,614,150 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.198% | 506 |
| Remaining individualsnot grpmax-eligible | 0.0896% | 1,116 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0844% | 1,184 |
| African / African-American | 0.0386% | 2,588 |
| Admixed American | 0.0217% | 4,616 |
| Finnishnot grpmax-eligible | 0.00781% | 12,807 |
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
- CASP14
- Protein
- p.Glu59=
- Coding
- c.177G>A
- MANE Select
- NM_012114
- dbSNP
- rs112231728
- Type
- single nucleotide variant
- Location
- chr19:15053631 (GRCh38)
- Gene constraint
- LOEUF 1.217 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.44
Similar variants
- CASP14 p.Glu59Gly Uncertain significance ★ ⚠ same residue
- CASP14 p.Met150Lys Uncertain significance ★★ ⚠ same type
- CASP14 p.Tyr240Phe Uncertain significance ★★ ⚠ same type
- CASP14 c.404-151A>C Benign ★★ same type
- CASP14 c.404-271T>C Benign ★★ same type
- CASP14 c.520+77T>C Benign ★★ same type
- CASP14 c.625-34G>T Benign ★★ same type
- CASP14 c.-46-101T>A Benign ★★ 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/casp14-p-glu59 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown