CPE p.Ala118Val
c.353C>T · VCV4686534
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.3702 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
0/2 damaging
REVEL, SaProt · AlphaMissense no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.3702 | ambiguous |
|---|---|---|
| REVEL | 0.211 | benign-leaning |
| SaProt | LLR -2.13 | tolerated |
| ⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP -0.71, phastCons 1 |
| Regional constraint | o/e 0.85 | unconstrained · MANE · 118 kb · p 0.00025 · regional, not allelic |
| Overall | ||
| CADD | 19.92 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- CPE
- Protein
- p.Ala118Val
- Coding
- c.353C>T
- MANE Select
- NM_001873
- Type
- single nucleotide variant
- Location
- chr4:165464435 (GRCh38)
- Gene constraint
- LOEUF 0.565 · pLI 0.83 (gnomAD)
- Structure
- AlphaFold pLDDT 90.83
- Residue 118
- the peptidase m14 domain
Similar variants
- CPE p.Ala118= Likely benign same residue
- CPE p.Arg121Ter Pathogenic ★★ same type
- CPE p.Arg262Trp Uncertain significance ★★ ⚠ same type
- CPE p.Arg297Trp Uncertain significance ★★ ⚠ same type
- CPE p.Asp251Gly Uncertain significance ★★ ⚠ same type
- CPE p.Asp304Ala Uncertain significance ★★ ⚠ same type
- CPE p.Trp21Cys Uncertain significance ★★ ⚠ same type
- CPE c.307+13C>T Likely 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/cpe-p-ala118val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown