Is CDH1 p.Asp313Glu (c.939C>G) pathogenic?

CDH1 p.Asp313Glu (c.939C>G) is classified Conflicting classifications of pathogenicity in CDH1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-09-23). AlphaMissense: likely benign (0.0828); Very rare (popmax 0.000169%, nfe); Associated with hereditary diffuse gastric adenocarcinoma.

What condition is associated with CDH1 p.Asp313Glu (c.939C>G)?

CDH1 p.Asp313Glu (c.939C>G) is associated with hereditary diffuse gastric adenocarcinoma, hereditary neoplastic syndrome (ClinVar).

How common is CDH1 p.Asp313Glu (c.939C>G) in the general population?

CDH1 p.Asp313Glu (c.939C>G) is very rare (popmax 0.000169%, nfe) (gnomAD).

How is Hereditary diffuse gastric cancer inherited?

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

What do computational predictors say about CDH1 p.Asp313Glu (c.939C>G)?

AlphaMissense predicts likely benign (score 0.0828) — an in-silico prediction, not a clinical call.

CDH1 p.Asp313Glu

c.939C>G · rs955528859 · VCV1362483

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0828 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary diffuse gastric adenocarcinoma

Computational evidence

Protein change
AlphaMissense	0.0828	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -6.05	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.3	GERP -3.6
Regional constraint	o/e 0.87	unconstrained · MANE · 25 kb · p 0.00015 · regional, not allelic
Overall
CADD	0.012	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,038 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,890 alleles · very rare

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.Asp313Glu
Coding: c.939C>G
MANE Select: NM_004360
dbSNP: rs955528859
Type: single nucleotide variant
Location: chr16:68811790 (GRCh38)
Gene constraint: LOEUF 0.514 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.13 · 22 PDB
Residue 313: the cadherin 2 domain

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.Asp313Val Uncertain significance ★★ ⚠ same residue
CDH1 p.Asp313= Benign/Likely benign ★★ same residue
CDH1 p.Asp313His Conflicting classifications of pathogenicity ★ ⚠ same residue
CDH1 p.Asp313Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
CDH1 p.Asp313Asn Likely benign ★ 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

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-asp313glu (accessed [today's date]).

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