Is CDH1 p.Gln16= (c.48G>A) pathogenic?

CDH1 p.Gln16= (c.48G>A) is classified Conflicting classifications of pathogenicity in CDH1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-03-17). Absent from gnomAD v4.1; Associated with hereditary diffuse gastric adenocarcinoma.

What condition is associated with CDH1 p.Gln16= (c.48G>A)?

CDH1 p.Gln16= (c.48G>A) is associated with hereditary diffuse gastric adenocarcinoma, hereditary neoplastic syndrome (ClinVar).

How common is CDH1 p.Gln16= (c.48G>A) in the general population?

CDH1 p.Gln16= (c.48G>A) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary diffuse gastric cancer inherited?

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

CDH1 p.Gln16=

c.48G>A · rs749591910 · VCV574809

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,537,622)

Conditions

hereditary diffuse gastric adenocarcinoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.65	donor loss · deltas
Pangolin	Δ0.54	loss · gain 0.07 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.9	GERP 2.2, phastCons 1
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,537,622). 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.Gln16=
Coding: c.48G>A
MANE Select: NM_004360
dbSNP: rs749591910
Type: single nucleotide variant
Location: chr16:68737463 (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.Gln16Ter Pathogenic ★★ same residue
CDH1 p.Gln16Arg Uncertain significance ★★ ⚠ same residue
CDH1 p.Gln16Leu Uncertain significance ★★ ⚠ same residue
CDH1 p.Gln16Glu Uncertain significance ★ ⚠ same residue
CDH1 p.Gln16His Conflicting classifications of pathogenicity ★ ⚠ same residue
CDH1 p.Gln16Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
CDH1 p.Gln16fs Pathogenic ★ same residue
CDH1 c.1008+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-gln16 (accessed [today's date]).

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