Is ALK c.788delG pathogenic?

ALK c.788delG is classified Uncertain significance in ALK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-07). Very rare (popmax 0.000169%, nfe); Associated with neuroblastoma, susceptibility to, 3.

What condition is associated with ALK c.788delG?

ALK c.788delG is associated with neuroblastoma, susceptibility to, 3, hereditary neoplastic syndrome (ClinVar).

How common is ALK c.788delG in the general population?

ALK c.788delG is very rare (popmax 0.000169%, nfe) (gnomAD).

ALK c.788delG

rs768588824 · VCV2174295

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

neuroblastoma, susceptibility to, 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP -5, phastCons 0.99
Non-coding constraint	Z -1.12	1 kb window · o/e 1.08 · regional · uncalibrated
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,978 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,914 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: ALK
Coding: c.788delG
MANE Select: NM_004304
dbSNP: rs768588824
Type: Deletion
Location: chr2:29695014 (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

Also linked: hereditary neoplastic syndrome

Similar variants

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
ALK p.Ile1522fs Uncertain significance ★★ same condition
ALK p.Phe1301fs 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-c-788delg (accessed [today's date]).

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