Is CDH1 p.Asn863= (c.2589C>T) pathogenic?

CDH1 p.Asn863= (c.2589C>T) is classified Conflicting classifications of pathogenicity in CDH1 (ClinVar, Conflicting submitters, 18 submitters; last evaluated 2026-02-03). Ultra-rare (popmax 0.041%, nfe); Associated with Breast and/or ovarian cancer.

What condition is associated with CDH1 p.Asn863= (c.2589C>T)?

CDH1 p.Asn863= (c.2589C>T) is associated with Breast and/or ovarian cancer, breast cancer, hereditary diffuse gastric adenocarcinoma (ClinVar).

How common is CDH1 p.Asn863= (c.2589C>T) in the general population?

CDH1 p.Asn863= (c.2589C>T) is ultra-rare (popmax 0.041%, nfe) (gnomAD).

CDH1 p.Asn863=

c.2589C>T · rs115817750 · VCV136067

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 18 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.041%, nfe)

Conditions

Breast and/or ovarian cancer

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 -7.6	GERP -3.9
Overall
CADD	4.587	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.041% European (non-Finnish) · 484/1,180,034 alleles

Filtering AF 0.038% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0367%

Overall 0.0328% 530/1,614,164 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.041%	2,438
Remaining individualsnot grpmax-eligible	0.0352%	2,841
African / African-American	0.024%	4,168
East Asian	0.00891%	11,222
South Asian	0.0022%	45,542

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.Asn863=
Coding: c.2589C>T
MANE Select: NM_004360
dbSNP: rs115817750
Type: single nucleotide variant
Location: chr16:68833439 (GRCh38)
Gene constraint: LOEUF 0.514 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.13 · 22 PDB
Residue 863: the 'required for binding alpha, beta and gamma catenins' region

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

Disease context

Breast and/or ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: breast cancer hereditary diffuse gastric adenocarcinoma hereditary neoplastic syndrome

Similar variants

CDH1 p.Asn863Lys 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
CDH1 c.1565+1G>T 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-asn863 (accessed [today's date]).

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