Is CDH1 p.Glu463Ter (c.1386dup) pathogenic?

CDH1 p.Glu463Ter (c.1386dup) is classified Pathogenic in CDH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-04). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with CDH1 p.Glu463Ter (c.1386dup)?

CDH1 p.Glu463Ter (c.1386dup) is associated with hereditary neoplastic syndrome (ClinVar).

How common is CDH1 p.Glu463Ter (c.1386dup) in the general population?

CDH1 p.Glu463Ter (c.1386dup) is absent from gnomAD (gnomAD).

CDH1 p.Glu463Ter

c.1386dup · rs2543930495 · VCV1771409

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 10 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.4	GERP 1, phastCons 0.001

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Glu463Ter
Coding: c.1386dup
MANE Select: NM_004360
dbSNP: rs2543930495
Type: Duplication
Location: chr16:68815576 (GRCh38)
Gene constraint: LOEUF 0.514 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.13 · 22 PDB
Residue 463: the cadherin 3 domain; a UniProt-annotated variant site (in a gastric carcinoma sample)

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.Glu463Lys Uncertain significance ★★ ⚠ same residue
CDH1 p.Glu463= Likely benign ★ same residue
CDH1 c.1565+2dup Pathogenic ★★★ same condition
CDH1 p.Ala530fs Pathogenic ★★★ same condition
CDH1 p.Arg796fs Likely pathogenic ★★★ same condition
CDH1 p.Asn174fs Pathogenic ★★★ same condition
CDH1 p.Gln677fs Pathogenic ★★★ same condition
CDH1 p.Gly579fs 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-glu463ter (accessed [today's date]).

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