Is ERBB2 c.2726del pathogenic?

ERBB2 c.2726del is classified Uncertain significance in ERBB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-07). Very rare (popmax 8.49e-05%, nfe); Associated with ovarian cancer.

What condition is associated with ERBB2 c.2726del?

ERBB2 c.2726del is associated with ovarian cancer, gastric cancer, lung cancer (ClinVar).

How common is ERBB2 c.2726del in the general population?

ERBB2 c.2726del is very rare (popmax 8.49e-05%, nfe) (gnomAD).

ERBB2 c.2726del

VCV3581937

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Conditions

ovarian cancer

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 11	GERP 2.6, phastCons 1
Non-coding constraint	Z 4.64	1 kb window · o/e 0.69 · regional · uncalibrated

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,178,404 alleles

Overall 6.86e-05% 1/1,458,410 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: ERBB2
Coding: c.2726del
MANE Select: NM_004448
Type: Deletion
Location: chr17:39725706 (GRCh38)
Gene constraint: LOEUF 0.518 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 74.65 · 63 PDB

Full ERBB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: gastric cancer lung cancer glioma susceptibility 1 visceral neuropathy, familial, 2, autosomal recessive

Similar variants

ERBB2 p.Gln1225_Asp1226del Conflicting classifications of pathogenicity ★ same condition
ERBB2 c.3412+1_3412+13del Likely pathogenic same condition
ERBB2 p.Ala598Asp Uncertain significance ★★ ⚠ same condition
ERBB2 p.Arg1048Cys Uncertain significance ★★ ⚠ same condition
ERBB2 p.Arg188Cys Uncertain significance ★★ ⚠ same condition
ERBB2 p.Arg190Gln Uncertain significance ★★ ⚠ same condition
ERBB2 p.Arg203His Uncertain significance ★★ ⚠ same condition
ERBB2 p.Arg217Cys Uncertain significance ★★ ⚠ 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/erbb2-c-2726del (accessed [today's date]).

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