Is ERBB2 p.Pro1162fs (c.3484_3485insG) pathogenic?

ERBB2 p.Pro1162fs (c.34843485insG) is classified Pathogenic in ERBB2 (ClinVar, No assertion criteria, 1 submitter). Absent from gnomAD; Associated with colorectal cancer.

What condition is associated with ERBB2 p.Pro1162fs (c.3484_3485insG)?

ERBB2 p.Pro1162fs (c.3484_3485insG) is associated with colorectal cancer (ClinVar).

How common is ERBB2 p.Pro1162fs (c.3484_3485insG) in the general population?

ERBB2 p.Pro1162fs (c.3484_3485insG) is absent from gnomAD (gnomAD).

ERBB2 p.Pro1162fs

c.3484_3485insG · rs2059860543 · VCV998138

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

colorectal cancer

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (27 of 27) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.3	GERP 0.25, 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.Pro1162fs
Coding: c.3484_3485insG
MANE Select: NM_004448
dbSNP: rs2059860543
Type: Insertion
Location: chr17:39727760 (GRCh38)
Gene constraint: LOEUF 0.518 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 74.65 · 63 PDB
Residue 1162: the 'disordered' region

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

Disease context

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

Similar variants

ERBB2 p.Pro1162Ser Uncertain significance ★ ⚠ same residue
ERBB2 p.Arg756Ser Uncertain significance ★★ ⚠ same condition
ERBB2 p.Gly537fs Pathogenic same condition
ERBB2 p.Ala775_Gly776insSerValMetAla Likely pathogenic ★ same type
ERBB2 p.Ile946fs Uncertain significance ★ same type
ERBB2 p.Gly776delinsValCys 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-pro1162fs (accessed [today's date]).

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