Is ALK p.Phe1301fs (c.3902del) pathogenic?

ALK p.Phe1301fs (c.3902del) is classified Uncertain significance in ALK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-05-10). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with ALK p.Phe1301fs (c.3902del)?

ALK p.Phe1301fs (c.3902del) is associated with hereditary neoplastic syndrome, neuroblastoma, susceptibility to, 3 (ClinVar).

How common is ALK p.Phe1301fs (c.3902del) in the general population?

ALK p.Phe1301fs (c.3902del) is absent from gnomAD (gnomAD).

ALK p.Phe1301fs

c.3902del · rs1669334076 · VCV1009087

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic syndrome

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 26 of 29
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.5, 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.Phe1301fs
Coding: c.3902del
MANE Select: NM_004304
dbSNP: rs1669334076
Type: Deletion
Location: chr2:29207207 (GRCh38)
Gene constraint: LOEUF 0.562 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.26 · 79 PDB
Residue 1301: an α-helix; the protein kinase domain

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neuroblastoma, susceptibility to, 3

Similar variants

ALK p.Phe1301Cys Uncertain significance ★ ⚠ same residue
ALK p.Phe1301Ile Uncertain significance ★ ⚠ same residue
ALK p.Phe1301Leu Uncertain significance ★ ⚠ same residue
ALK p.Phe1301= Likely benign ★ 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

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-phe1301fs (accessed [today's date]).

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