CDH1 p.Glu880=
c.2640G>A · rs864622218 · VCV219712
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000339%, nfe)
Conditions
3
hereditary neoplastic syndrome
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 3.1 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 9.104 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000339%
European (non-Finnish) · 4/1,179,864 alleles
Filtering AF
7.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.4e-05%
Overall
0.000274%
4/1,461,308 alleles · very rare
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
- CDH1
- Protein
- p.Glu880=
- Coding
- c.2640G>A
- MANE Select
- NM_004360
- dbSNP
- rs864622218
- Type
- single nucleotide variant
- Location
- chr16:68833490 (GRCh38)
- Gene constraint
- LOEUF 0.514 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 79.13 · 22 PDB
- Residue 880
- the 'required for binding alpha, beta and gamma catenins' region; a UniProt-annotated variant site (in)
Similar variants
- CDH1 p.Glu880Lys Benign ★★★ ⚠ same residue
- CDH1 p.Glu880Gln Uncertain significance ★★ ⚠ same residue
- CDH1 p.Glu880Gly Uncertain significance ★★ ⚠ same residue
- CDH1 c.1008+2T>C Likely pathogenic ★★★ same condition
- CDH1 c.1137+1G>A Pathogenic ★★★ same condition
- CDH1 c.1137+2T>C Likely pathogenic ★★★ same condition
- CDH1 c.1320+1G>C Likely pathogenic ★★★ same condition
- CDH1 c.1565+1G>A Pathogenic ★★★ same condition
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/cdh1-p-glu880 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown