Is ERBB2 p.Leu755Pro (c.2263_2264delinsCC) pathogenic?

ERBB2 p.Leu755Pro (c.22632264delinsCC) is classified Pathogenic/Likely pathogenic in ERBB2 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2004-09-30). Absent from gnomAD; Associated with lung adenocarcinoma.

What condition is associated with ERBB2 p.Leu755Pro (c.2263_2264delinsCC)?

ERBB2 p.Leu755Pro (c.2263_2264delinsCC) is associated with lung adenocarcinoma (ClinVar).

How common is ERBB2 p.Leu755Pro (c.2263_2264delinsCC) in the general population?

ERBB2 p.Leu755Pro (c.2263_2264delinsCC) is absent from gnomAD (gnomAD).

ERBB2 p.Leu755Pro

c.2263_2264delinsCC · rs121913469 · VCV13877

Pathogenic/Likely pathogenic No assertion criteria

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

lung 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 5.1	GERP 0.69, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 2,325 bp · p 1.2e-20 · 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.

Cancer therapy — CIViC

Disease	Therapies	Level	Significance
Lung Non-small Cell Carcinoma	Trastuzumab Deruxtecan	A	Sensitivity/Response
Lung Non-small Cell Carcinoma	Osimertinib	C	Sensitivity/Response
Lung Non-small Cell Carcinoma	Zongertinib	A	Sensitivity/Response
Cancer	Lapatinib	D	Resistance

Variant & gene context

Gene: ERBB2
Protein: p.Leu755Pro
Coding: c.2263_2264delinsCC
MANE Select: NM_004448
dbSNP: rs121913469
Type: Indel
Location: chr17:39723966 (GRCh38)
Gene constraint: LOEUF 0.518 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 74.65 · 63 PDB
Residue 755: a β-strand; the protein kinase domain; a UniProt-annotated variant site (in lncr; uncertain significance; somatic mutation)

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

Disease context

lung adenocarcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ERBB2 p.Gly778_Pro780dup Pathogenic ★ same condition
ERBB2 p.Tyr772_Ala775dup Likely pathogenic ★ same condition
ERBB2 p.Leu869Arg Pathogenic same condition
ERBB2 p.Val777_Ser779dup Pathogenic same condition
ERBB2 p.Gly776delinsLeuCys Likely pathogenic ★ same type
ERBB2 c.3405_3412+42delinsAG Uncertain significance ★ same type

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-p-leu755pro (accessed [today's date]).

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