CDH1 p.Val202Ile
c.604G>A · rs546716073 · VCV133853
ClinGen expert panel — CDH1 VCEP
Benign for CDH1-related diffuse gastric and lobular breast cancer. Applied ACMG criteria (verbatim):
BA1
Curation rationale (ClinGen, verbatim)
The c.604G>A (p.Val202Ile) variant has an allele frequency of 0.00354 (0.35%, 109/30,772 alleles) in the South Asian subpopulation of the gnomAD cohort (BA1). In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BA1.
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| AlphaMissense | 0.0795 | likely benign |
|---|---|---|
| REVEL | 0.064 | moderately benign-leaning |
| SaProt | LLR -8.56 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.6 | GERP 0.98, phastCons 0.095 |
| Regional constraint | o/e 0.87 | unconstrained · MANE · 25 kb · p 0.00015 · regional, not allelic |
| Overall | ||
| CADD | 14.51 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.352% | 284 |
| Remaining individualsnot grpmax-eligible | 0.0368% | 2,718 |
| East Asian | 0.0312% | 3,206 |
| Middle Eastern | 0.0165% | 6,062 |
| Admixed American | 0.00167% | 60,006 |
| European (non-Finnish) | 8.47e-05% | 1,180,004 |
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.Val202Ile
- Coding
- c.604G>A
- MANE Select
- NM_004360
- dbSNP
- rs546716073
- Type
- single nucleotide variant
- Location
- chr16:68808765 (GRCh38)
- Gene constraint
- LOEUF 0.514 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 79.13 · 22 PDB
- Residue 202
- the cadherin 1 domain
Similar variants
- CDH1 p.Val202Leu Uncertain significance ★★★ ⚠ same residue
- CDH1 p.Val202= Benign/Likely benign ★★ same residue
- CDH1 p.Val202Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
- CDH1 p.Val202fs Pathogenic ★ 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-val202ile (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown