Is ERBB2 c.73+17del pathogenic?

ERBB2 c.73+17del is classified Benign in ERBB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-15). Very rare (popmax 0.000281%, nfe).

How common is ERBB2 c.73+17del in the general population?

ERBB2 c.73+17del is very rare (popmax 0.000281%, nfe) (gnomAD).

ERBB2 c.73+17del

rs1294271877 · VCV2902637

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000281%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +17	near-intronic (+17 nt from the splice site)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.1	GERP -0.33
Non-coding constraint	Z 3.76	1 kb window · o/e 0.77 · regional · uncalibrated

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000281% European (non-Finnish) · 3/1,067,832 alleles

Filtering AF 7.5e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.1e-05%

Overall 0.000244% 3/1,228,950 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.73+17del
MANE Select: NM_004448
dbSNP: rs1294271877
Type: Deletion
Location: chr17:39700325 (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

Similar variants

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.Pro128fs Uncertain significance ★ 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
ERBB2 c.1738-3del 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-c-73-plus-17del (accessed [today's date]).

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