CDH1 p.Ala817=
c.2451G>A · rs149450874 · VCV183842
ClinGen expert panel — CDH1 VCEP
Likely Benign for CDH1-related diffuse gastric and lobular breast cancer. Applied ACMG criteria (verbatim):
BS2 BP7
Curation rationale (ClinGen, verbatim)
The c.2451G>A variant is predicted silent and has been observed in >10 individuals without a diagnosis of diffuse gastric cancer, signet ring tumor or lobular breast cancer and whose family histories do not suggest HDGC (BS2; internal laboratory contributors). The nucleotide is not conserved (BP7). Therefore, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BS2, BP7.
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
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 -5.5 | GERP -3.9 |
| Overall | ||
| CADD | 1.008 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0178% | 5,611 |
| European (non-Finnish) | 0.0169% | 5,900 |
| African / African-American | 0.0107% | 9,378 |
| Admixed American | 0.00833% | 12,002 |
| South Asian | 0.00549% | 18,217 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,836 |
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.Ala817=
- Coding
- c.2451G>A
- MANE Select
- NM_004360
- dbSNP
- rs149450874
- Type
- single nucleotide variant
- Location
- chr16:68833301 (GRCh38)
- Gene constraint
- LOEUF 0.514 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 79.13 · 22 PDB
- Residue 817
- the 'required for binding alpha, beta and gamma catenins' region
Similar variants
- CDH1 p.Ala817Val Likely benign ★★★ same residue
- CDH1 p.Ala817Pro Uncertain significance ★★ ⚠ same residue
- CDH1 p.Ala817Glu Uncertain significance ★ ⚠ same residue
- CDH1 p.Ala817Thr 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
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-ala817 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown