Is CDH1 p.Asp764= (c.2292C>T) pathogenic?

CDH1 p.Asp764= (c.2292C>T) is classified Benign/Likely benign in CDH1 (ClinVar, Multiple submitters, 27 submitters; last evaluated 2026-06-01). Rare (popmax 0.34%, sas); Associated with Breast and/or ovarian cancer.

What condition is associated with CDH1 p.Asp764= (c.2292C>T)?

CDH1 p.Asp764= (c.2292C>T) is associated with Breast and/or ovarian cancer, breast cancer, hereditary diffuse gastric adenocarcinoma (ClinVar).

How common is CDH1 p.Asp764= (c.2292C>T) in the general population?

CDH1 p.Asp764= (c.2292C>T) is rare (popmax 0.34%, sas) (gnomAD).

CDH1 p.Asp764=

c.2292C>T · rs61747636 · VCV136699

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 27 submitters

gnomAD v4.1

Rare

rare (popmax 0.34%, sas)

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 -0.028	GERP -0.068, phastCons 0.72
Overall
CADD	7.021	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.34% South Asian · 310/91,076 alleles

Filtering AF 0.309% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.297%

Overall 0.259% 4,180/1,613,944 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.34%	294
European (non-Finnish)	0.299%	334
Remaining individualsnot grpmax-eligible	0.235%	425
Admixed American	0.205%	488
Middle Eastern	0.198%	505
Amishnot grpmax-eligible	0.11%	912
Ashkenazi Jewishnot grpmax-eligible	0.0878%	1,139
African / African-American	0.0373%	2,679
Finnishnot grpmax-eligible	0.00312%	32,003
East Asian	0.00223%	44,868

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.Asp764=
Coding: c.2292C>T
MANE Select: NM_004360
dbSNP: rs61747636
Type: single nucleotide variant
Location: chr16:68828301 (GRCh38)
Gene constraint: LOEUF 0.514 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.13 · 22 PDB
Residue 764: the 'disordered' region; the 'required for binding ctnnd1 and psen1' 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 prostate cancer hereditary neoplastic syndrome

Similar variants

CDH1 p.Asp764Gly Uncertain significance ★★ ⚠ same residue
CDH1 p.Asp764Val Uncertain significance ★★ ⚠ same residue
CDH1 p.Asp764Asn Uncertain significance ★ ⚠ same residue
CDH1 p.Asp764Glu 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-asp764 (accessed [today's date]).

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