Is ERBB2 p.Met774fs (c.2320del) pathogenic?

ERBB2 p.Met774fs (c.2320del) is classified Likely pathogenic in ERBB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2011-11-10). Absent from gnomAD; Associated with non-small cell lung carcinoma.

What condition is associated with ERBB2 p.Met774fs (c.2320del)?

ERBB2 p.Met774fs (c.2320del) is associated with non-small cell lung carcinoma (ClinVar).

How common is ERBB2 p.Met774fs (c.2320del) in the general population?

ERBB2 p.Met774fs (c.2320del) is absent from gnomAD (gnomAD).

ERBB2 p.Met774fs

c.2320del · rs397516978 · VCV44986

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

non-small cell lung carcinoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 20 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.6	GERP 0.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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: ERBB2
Protein: p.Met774fs
Coding: c.2320del
MANE Select: NM_004448
dbSNP: rs397516978
Type: Deletion
Location: chr17:39724738 (GRCh38)
Gene constraint: LOEUF 0.518 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 74.65 · 63 PDB
Residue 774: an α-helix; 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

non-small cell lung carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ERBB2 p.Ala775_Gly776insSerValMetAla Likely pathogenic ★ same condition
ERBB2 p.Gly776delinsLeuCys Likely pathogenic ★ same condition
ERBB2 p.Gly778_Pro780dup Pathogenic ★ same condition
ERBB2 p.Tyr772_Ala775dup Likely pathogenic ★ same condition
ERBB2 c.2726del Uncertain significance ★ same type
ERBB2 p.Gln1225_Asp1226del Conflicting classifications of pathogenicity ★ same type
ERBB2 p.Pro128fs Uncertain significance ★ same type
ERBB2 p.Thr718fs 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-met774fs (accessed [today's date]).

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