Is ALK p.Arg100fs (c.270_297dup) pathogenic?

ALK p.Arg100fs (c.270297dup) is classified Uncertain significance in ALK (ClinVar, Single submitter, 1 submitter; last evaluated 2017-06-21). No gnomAD frequency available for this variant; Associated with neuroblastoma, susceptibility to, 3.

What condition is associated with ALK p.Arg100fs (c.270_297dup)?

ALK p.Arg100fs (c.270_297dup) is associated with neuroblastoma, susceptibility to, 3 (ClinVar).

How common is ALK p.Arg100fs (c.270_297dup) in the general population?

ALK p.Arg100fs (c.270_297dup) is no gnomAD frequency available for this variant (gnomAD).

ALK p.Arg100fs

c.270_297dup · rs1553380382 · VCV470801

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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 1 of 29
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.1	GERP -3.5, phastCons 0.008

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.Arg100fs
Coding: c.270_297dup
MANE Select: NM_004304
dbSNP: rs1553380382
Type: Duplication
Location: chr2:29920362 (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.Arg100Gly Uncertain significance ★★ ⚠ same residue
ALK p.Arg100Lys Uncertain significance ★ ⚠ same residue
ALK c.3445_3450+13dup Uncertain significance ★★ same condition
ALK c.3938+5dup Uncertain significance ★★ same condition
ALK p.Ile1105dup Uncertain significance ★★ same condition
ALK p.Lys1525_Glu1526insAspProIleAlaLysLys Uncertain significance ★★ same condition
ALK p.Lys748_Asn749insGlyGlyLys Uncertain significance ★★ same condition
ALK p.Pro307_Gly308insAla 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-arg100fs (accessed [today's date]).

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