Is ALK p.Pro1027fs (c.3080del) pathogenic?

ALK p.Pro1027fs (c.3080del) is classified Uncertain significance in ALK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-17). Associated with neuroblastoma, susceptibility to, 3.

What condition is associated with ALK p.Pro1027fs (c.3080del)?

ALK p.Pro1027fs (c.3080del) is associated with neuroblastoma, susceptibility to, 3 (ClinVar).

ALK p.Pro1027fs

c.3080del · VCV4713242

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

neuroblastoma, susceptibility to, 3

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 19 of 29
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.9	GERP -2.7

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

Variant & gene context

Gene: ALK
Protein: p.Pro1027fs
Coding: c.3080del
MANE Select: NM_004304
Type: Deletion
Location: chr2:29225553 (GRCh38)
Gene constraint: LOEUF 0.562 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.26 · 79 PDB

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

Disease context

neuroblastoma, susceptibility to, 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ALK p.Pro1027= Likely benign ★★ same residue
ALK p.Pro1027Gln Uncertain significance ★ ⚠ same residue
ALK p.Pro1027Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
ALK c.788delG Uncertain significance ★★ same condition
ALK p.Arg918del Uncertain significance ★★ same condition
ALK p.Asn945fs Uncertain significance ★★ same condition
ALK p.Asp602fs Uncertain significance ★★ same condition
ALK p.Cys928_Gly934del Uncertain significance ★★ same condition

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/alk-p-pro1027fs (accessed [today's date]).

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