Is CDH1 p.Cys603= (c.1809T>C) pathogenic?

CDH1 p.Cys603= (c.1809T>C) is classified Likely benign in CDH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-11). Very rare (popmax 8.48e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with CDH1 p.Cys603= (c.1809T>C)?

CDH1 p.Cys603= (c.1809T>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is CDH1 p.Cys603= (c.1809T>C) in the general population?

CDH1 p.Cys603= (c.1809T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

CDH1 p.Cys603=

c.1809T>C · rs749802488 · VCV3224159

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

hereditary neoplastic 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 0.75	GERP -1.1, phastCons 1
Overall
CADD	2.781	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,908 alleles

Overall 6.2e-05% 1/1,614,056 alleles · very rare exomes 1/1,461,752 · genomes 0/152,304 · joint denominator

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.Cys603=
Coding: c.1809T>C
MANE Select: NM_004360
dbSNP: rs749802488
Type: single nucleotide variant
Location: chr16:68822098 (GRCh38)
Gene constraint: LOEUF 0.514 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.13 · 22 PDB
Residue 603: the cadherin 5 domain; a β-strand

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

Disease context

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

Similar variants

CDH1 p.Cys603Tyr Uncertain significance ★★ ⚠ same residue
CDH1 p.Cys603Arg Uncertain significance ★ ⚠ same residue
CDH1 p.Cys603Ser 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.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-cys603 (accessed [today's date]).

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