Is ERBB2 p.Pro128fs (c.383_384del) pathogenic?

ERBB2 p.Pro128fs (c.383384del) is classified Uncertain significance in ERBB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-17). Absent from gnomAD.

How common is ERBB2 p.Pro128fs (c.383_384del) in the general population?

ERBB2 p.Pro128fs (c.383_384del) is absent from gnomAD (gnomAD).

ERBB2 p.Pro128fs

c.383_384del · rs2145444620 · VCV1484619

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 3 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.62	GERP -5

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.Pro128fs
Coding: c.383_384del
MANE Select: NM_004448
dbSNP: rs2145444620
Type: Deletion
Location: chr17:39708478 (GRCh38)
Gene constraint: LOEUF 0.518 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 74.65 · 63 PDB
Residue 128: an α-helix

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

Similar variants

ERBB2 p.Pro128Arg Uncertain significance ★★ ⚠ same residue
ERBB2 p.Pro128Ala Uncertain significance ★ ⚠ same residue
ERBB2 p.Met774fs Likely pathogenic ★ same type
ERBB2 c.2726del Uncertain significance ★ same type
ERBB2 p.Gln1225_Asp1226del Conflicting classifications of pathogenicity ★ same type
ERBB2 p.Thr718fs Uncertain significance ★ same type
ERBB2 c.1021+9del Likely benign ★ same type
ERBB2 c.1314-16del Likely benign ★ 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-pro128fs (accessed [today's date]).

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