Is CDH1 p.Thr279Asp (c.835_836delinsGA) pathogenic?

CDH1 p.Thr279Asp (c.835836delinsGA) is classified Uncertain significance in CDH1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-09-01). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with CDH1 p.Thr279Asp (c.835_836delinsGA)?

CDH1 p.Thr279Asp (c.835_836delinsGA) is associated with hereditary neoplastic syndrome, hereditary diffuse gastric adenocarcinoma (ClinVar).

How common is CDH1 p.Thr279Asp (c.835_836delinsGA) in the general population?

CDH1 p.Thr279Asp (c.835_836delinsGA) is absent from gnomAD (gnomAD).

CDH1 p.Thr279Asp

c.835_836delinsGA · rs1960834189 · VCV1000887

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 neoplastic syndrome

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 8.2	GERP 1.8, phastCons 1
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.Thr279Asp
Coding: c.835_836delinsGA
MANE Select: NM_004360
dbSNP: rs1960834189
Type: Indel
Location: chr16:68811686 (GRCh38)
Gene constraint: LOEUF 0.514 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.13 · 22 PDB
Residue 279: the cadherin 2 domain

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

Also linked: hereditary diffuse gastric adenocarcinoma

Similar variants

CDH1 p.Thr279Ala Uncertain significance ★★ ⚠ same residue
CDH1 p.Thr279Ser Uncertain significance ★★ ⚠ same residue
CDH1 p.Thr279Asn Uncertain significance ★ ⚠ same residue
CDH1 p.Thr279Ile Uncertain significance ★ ⚠ same residue
CDH1 p.Thr279Pro Uncertain significance ★ ⚠ same residue
CDH1 p.Thr279= 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-thr279asp (accessed [today's date]).

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