Is CDH1 p.Ala530= (c.1590C>T) pathogenic?

CDH1 p.Ala530= (c.1590C>T) is classified Benign/Likely benign in CDH1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-09-19). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with CDH1 p.Ala530= (c.1590C>T)?

CDH1 p.Ala530= (c.1590C>T) is associated with hereditary neoplastic syndrome, hereditary diffuse gastric adenocarcinoma (ClinVar).

How common is CDH1 p.Ala530= (c.1590C>T) in the general population?

CDH1 p.Ala530= (c.1590C>T) is absent from gnomAD v4.1 (gnomAD).

CDH1 p.Ala530=

c.1590C>T · rs786201805 · VCV184940

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.41	GERP -0.11, phastCons 0.97
Overall
CADD	6.192	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDH1
Protein: p.Ala530=
Coding: c.1590C>T
MANE Select: NM_004360
dbSNP: rs786201805
Type: single nucleotide variant
Location: chr16:68819304 (GRCh38)
Gene constraint: LOEUF 0.514 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.13 · 22 PDB
Residue 530: the cadherin 4 domain

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

Also linked: hereditary diffuse gastric adenocarcinoma

Similar variants

CDH1 p.Ala530Val Uncertain significance ★★ ⚠ same residue
CDH1 p.Ala530Pro Uncertain significance ★ ⚠ same residue
CDH1 p.Ala530fs Pathogenic ★★★ same residue
CDH1 p.Ala530Phe 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-ala530 (accessed [today's date]).

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