Is CDH1 p.Ala137Arg (c.409_410delinsAG) pathogenic?

CDH1 p.Ala137Arg (c.409410delinsAG) is classified Uncertain significance in CDH1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-07-25). Absent from gnomAD; Associated with hereditary diffuse gastric adenocarcinoma.

What condition is associated with CDH1 p.Ala137Arg (c.409_410delinsAG)?

CDH1 p.Ala137Arg (c.409_410delinsAG) is associated with hereditary diffuse gastric adenocarcinoma, hereditary neoplastic syndrome (ClinVar).

How common is CDH1 p.Ala137Arg (c.409_410delinsAG) in the general population?

CDH1 p.Ala137Arg (c.409_410delinsAG) 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.Ala137Arg

c.409_410delinsAG · rs2543914394 · VCV2587431

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

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 -1	GERP -5
Regional constraint	o/e 1.05	unconstrained · MANE · 71 kb · p 0.52 · 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.Ala137Arg
Coding: c.409_410delinsAG
MANE Select: NM_004360
dbSNP: rs2543914394
Type: Indel
Location: chr16:68808445 (GRCh38)
Gene constraint: LOEUF 0.514 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.13 · 22 PDB

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

Also linked: hereditary neoplastic syndrome

For Hereditary diffuse gastric cancer (Orphanet):

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

Similar variants

CDH1 p.Ala137Glu Uncertain significance ★★ ⚠ same residue
CDH1 p.Ala137fs Pathogenic ★ same residue
CDH1 p.Ala137Gly Uncertain significance ★ ⚠ same residue
CDH1 p.Ala137Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
CDH1 p.Ala137Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
CDH1 p.Ala137Val Uncertain significance ★ ⚠ 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-ala137arg (accessed [today's date]).

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