CDH1 p.Arg800fs
c.2398del · rs587783048 · VCV156497
ClinGen expert panel — CDH1 VCEP
Pathogenic for CDH1-related diffuse gastric and lobular breast cancer. Applied ACMG criteria (verbatim):
PVS1_Strong PM2_Supporting PS4 PP1
Curation rationale (ClinGen, verbatim)
The c.2398delC (p.Arg800Alafs*16) variant is predicted to result in a premature stop codon that leads to a truncated protein. However, it is located within the nonsense mediated decay resistance region upstream of c.2506G>T (p.Glu836*) (PVS1_Strong). The variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has been reported in at least 4 families meeting HDGC clinical criteria (PS4; PMID 17545690). This variant was also found to co-segregation with disease in multiple affected family members, with 3 or 4 meioses observed (PP1; PMID: 17545690). In summary, this variant meets criteria to be classified as pathogenic based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): PVS1_Strong, PM2_Supporting, PS4, PP1.
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. | ||
| Consequence | frameshift | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | escapes | premature termination codon within the last 50 nt of the penultimate exon (15 of 16, 44 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -2.3 | GERP -3.5 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.
Variant & gene context
- Gene
- CDH1
- Protein
- p.Arg800fs
- Coding
- c.2398del
- MANE Select
- NM_004360
- dbSNP
- rs587783048
- Type
- Deletion
- Location
- chr16:68829753 (GRCh38)
- Gene constraint
- LOEUF 0.514 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 79.13 · 22 PDB
Similar variants
- CDH1 p.Arg800His Benign ★★★ same residue
- CDH1 p.Arg800Cys Uncertain significance ★★ ⚠ same residue
- CDH1 p.Arg800Leu Uncertain significance ★★ ⚠ same residue
- CDH1 p.Arg800= Benign/Likely benign ★★ same residue
- CDH1 p.Arg800Pro Uncertain significance ★ ⚠ same residue
- CDH1 c.1137+1del Pathogenic ★★★ same condition
- CDH1 c.1565+1del Likely pathogenic ★★★ same condition
- CDH1 c.1711+2_1711+7del 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-arg800fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown