Is CDH1 p.Ala617Arg (c.1849_1850delinsAG) pathogenic?

CDH1 p.Ala617Arg (c.18491850delinsAG) is classified Uncertain significance in CDH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-11). Absent from gnomAD; Associated with hereditary diffuse gastric adenocarcinoma.

What condition is associated with CDH1 p.Ala617Arg (c.1849_1850delinsAG)?

CDH1 p.Ala617Arg (c.1849_1850delinsAG) is associated with hereditary diffuse gastric adenocarcinoma (ClinVar).

How common is CDH1 p.Ala617Arg (c.1849_1850delinsAG) in the general population?

CDH1 p.Ala617Arg (c.1849_1850delinsAG) is absent from gnomAD (gnomAD).

How is Hereditary diffuse gastric cancer inherited?

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

CDH1 p.Ala617Arg

c.1849_1850delinsAG · rs2152138443 · VCV1360286

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary diffuse gastric adenocarcinoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.8	GERP -0.059, phastCons 0.33
Regional constraint	o/e 0.87	unconstrained · MANE · 25 kb · p 0.00015 · regional, not allelic

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.Ala617Arg
Coding: c.1849_1850delinsAG
MANE Select: NM_004360
dbSNP: rs2152138443
Type: Indel
Location: chr16:68822138 (GRCh38)
Gene constraint: LOEUF 0.514 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.13 · 22 PDB
Residue 617: the cadherin 5 domain; a UniProt-annotated variant site (detected in an endometrial cancer sample; loss of heterozygosity; cells exhibited an intermediate phenotype concerning aggregation invasiveness and migration in vitro compared to cells transfected with wild-type sequence)

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

Disease context

hereditary diffuse gastric adenocarcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary diffuse gastric cancer (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

CDH1 p.Ala617Thr Benign ★★★ same residue
CDH1 p.Ala617fs Pathogenic ★★ same residue
CDH1 p.Ala617Ser Uncertain significance ★★ ⚠ same residue
CDH1 p.Ala617Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
CDH1 p.Ala617Val Conflicting classifications of pathogenicity ★ ⚠ same residue
CDH1 p.Ala617= Likely benign ★ same residue
CDH1 p.Pro42fs Pathogenic ★★★ same condition
CDH1 p.Asp514_Thr522delinsValTer Pathogenic/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-ala617arg (accessed [today's date]).

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