Is ALK p.Gly562fs (c.1684_1685del) pathogenic?

ALK p.Gly562fs (c.16841685del) is classified Conflicting classifications of pathogenicity in ALK (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-30). Absent from gnomAD; Associated with neuroblastoma, susceptibility to, 3.

What condition is associated with ALK p.Gly562fs (c.1684_1685del)?

ALK p.Gly562fs (c.1684_1685del) is associated with neuroblastoma, susceptibility to, 3, hereditary neoplastic syndrome (ClinVar).

How common is ALK p.Gly562fs (c.1684_1685del) in the general population?

ALK p.Gly562fs (c.1684_1685del) is absent from gnomAD (gnomAD).

ALK p.Gly562fs

c.1684_1685del · rs1666207064 · VCV1482321

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 9 of 29
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.4	GERP -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: ALK
Protein: p.Gly562fs
Coding: c.1684_1685del
MANE Select: NM_004304
dbSNP: rs1666207064
Type: Deletion
Location: chr2:29297020 (GRCh38)
Gene constraint: LOEUF 0.562 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.26 · 79 PDB
Residue 562: the mam 2 domain

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

Also linked: hereditary neoplastic syndrome

Similar variants

ALK p.Gly562Val Uncertain significance ★ ⚠ 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
ALK p.Glu1409_Lys1410del Uncertain significance ★★ same condition
ALK p.Glu1433fs 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-gly562fs (accessed [today's date]).

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