Is CDH1 p.Ile650= (c.1950C>T) pathogenic?

CDH1 p.Ile650= (c.1950C>T) is classified Benign/Likely benign in CDH1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-17). Absent from gnomAD v4.1; Associated with hereditary breast carcinoma.

What condition is associated with CDH1 p.Ile650= (c.1950C>T)?

CDH1 p.Ile650= (c.1950C>T) is associated with hereditary breast carcinoma, hereditary diffuse gastric adenocarcinoma, ovarian cancer (ClinVar).

How common is CDH1 p.Ile650= (c.1950C>T) in the general population?

CDH1 p.Ile650= (c.1950C>T) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary breast cancer inherited?

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

CDH1 p.Ile650=

c.1950C>T · rs786202320 · VCV185620

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,611,612)

Conditions

hereditary breast carcinoma

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 0.37	GERP 0.047, phastCons 0.016
Overall
CADD	11.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,611,612). 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.Ile650=
Coding: c.1950C>T
MANE Select: NM_004360
dbSNP: rs786202320
Type: single nucleotide variant
Location: chr16:68823412 (GRCh38)
Gene constraint: LOEUF 0.514 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.13 · 22 PDB
Residue 650: 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 carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

For Hereditary breast cancer (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult, Elderly

Similar variants

CDH1 p.Ile650Thr Uncertain significance ★★ ⚠ same residue
CDH1 p.Ile650Val Uncertain significance ★ ⚠ same residue
CDH1 p.Ile650fs Pathogenic ★★★ 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

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-ile650 (accessed [today's date]).

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