Is CDH1 p.Pro625fs (c.1872_1878del) pathogenic?

CDH1 p.Pro625fs (c.18721878del) is classified Likely pathogenic in CDH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-01). Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with CDH1 p.Pro625fs (c.1872_1878del)?

CDH1 p.Pro625fs (c.1872_1878del) is associated with hereditary breast ovarian cancer syndrome (ClinVar).

How is Hereditary breast and/or ovarian cancer syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

CDH1 p.Pro625fs

c.1872_1878del · VCV4082382

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

hereditary breast ovarian cancer syndrome

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	predicted	premature termination codon in exon 12 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -5.8	GERP -3.6

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: CDH1
Protein: p.Pro625fs
Coding: c.1872_1878del
MANE Select: NM_004360
Type: Deletion
Location: chr16:68822159 (GRCh38)
Gene constraint: LOEUF 0.514 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.13 · 22 PDB
Residue 625: the cadherin 5 domain; a β-strand

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

Disease context

hereditary breast ovarian cancer syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary breast and/or ovarian cancer syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

CDH1 p.Pro625Ala Uncertain significance ★★ ⚠ same residue
CDH1 p.Pro625Leu Uncertain significance ★★ ⚠ same residue
CDH1 p.Ile300fs Likely pathogenic ★ same condition
CDH1 p.Pro625= Likely benign ★ same residue
CDH1 c.1565+1G>A Pathogenic ★★★ same condition
CDH1 p.Arg749Trp Uncertain significance ★★★ ⚠ same condition
CDH1 p.Asp72Asn Likely benign ★★★ ⚠ same condition
CDH1 p.Glu781Asp Likely benign ★★★ 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-pro625fs (accessed [today's date]).

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