CPEB2 p.Ala540Val
c.1619C>T · VCV3835860
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00222%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.075 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 6.5 | GERP 0.42, phastCons 1 |
| Regional constraint | o/e 1.34 | unconstrained · MANE · 50 kb · p 8.8e-28 · regional, not allelic |
| Overall | ||
| CADD | 23.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00222%
Admixed American · 1/45,030 alleles
Filtering AF
0.000258%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000746%
10/1,341,274 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00222% | 45,030 |
| Remaining individualsnot grpmax-eligible | 0.00173% | 57,836 |
| South Asian | 0.00125% | 80,314 |
| European (non-Finnish) | 0.00062% | 161,357 |
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
- CPEB2
- Protein
- p.Ala540Val
- Coding
- c.1619C>T
- MANE Select
- NM_001177382
- Type
- single nucleotide variant
- Location
- chr4:15004292 (GRCh38)
- Gene constraint
- LOEUF 1.328 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 61.86
Similar variants
- CPEB2 p.Ala113Val Uncertain significance ★ same type
- CPEB2 p.Ala27Val Uncertain significance ★ same type
- CPEB2 p.Ala287Ser Uncertain significance ★ same type
- CPEB2 p.Ala288Val Uncertain significance ★ same type
- CPEB2 p.Ala494Ser Uncertain significance ★ same type
- CPEB2 p.Ala517Thr Uncertain significance ★ same type
- CPEB2 p.Ala541Thr Uncertain significance ★ same type
- CPEB2 p.Ala73Glu 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/cpeb2-p-ala540val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown