Is CDH1 p.Pro804= (c.2412C>T) pathogenic?

CDH1 p.Pro804= (c.2412C>T) is classified Conflicting classifications of pathogenicity in CDH1 (ClinVar, Conflicting submitters, 15 submitters; last evaluated 2026-01-31). Ultra-rare (popmax 0.0534%, amr); Associated with CDH1-related diffuse gastric and lobular breast cancer syndrome.

What condition is associated with CDH1 p.Pro804= (c.2412C>T)?

CDH1 p.Pro804= (c.2412C>T) is associated with CDH1-related diffuse gastric and lobular breast cancer syndrome, hereditary diffuse gastric adenocarcinoma, hereditary neoplastic syndrome (ClinVar).

How common is CDH1 p.Pro804= (c.2412C>T) in the general population?

CDH1 p.Pro804= (c.2412C>T) is ultra-rare (popmax 0.0534%, amr) (gnomAD).

CDH1 p.Pro804=

c.2412C>T · rs202075199 · VCV183811

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 15 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0534%, amr)

Conditions

CDH1-related diffuse gastric and lobular breast cancer 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 -3.3	GERP -3.5
Overall
CADD	4.475	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0534% Admixed American · 32/59,978 alleles

Filtering AF 0.0388% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0339%

Overall 0.00787% 127/1,613,942 alleles · ultra-rare exomes 93/1,461,862 · genomes 34/152,080 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0534%	1,874
African / African-American	0.02%	4,998
Remaining individualsnot grpmax-eligible	0.0096%	10,417
European (non-Finnish)	0.0061%	16,389
South Asian	0.0022%	45,530

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.Pro804=
Coding: c.2412C>T
MANE Select: NM_004360
dbSNP: rs202075199
Type: single nucleotide variant
Location: chr16:68829770 (GRCh38)
Gene constraint: LOEUF 0.514 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.13 · 22 PDB

Full CDH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Also linked: hereditary diffuse gastric adenocarcinoma hereditary neoplastic syndrome

Similar variants

CDH1 p.Pro804His Uncertain significance ★★ ⚠ same residue
CDH1 p.Pro804Ser 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
CDH1 c.1565+1G>C 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-pro804 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown