Is ALK p.Ser895fs (c.2682dup) pathogenic?

ALK p.Ser895fs (c.2682dup) is classified Conflicting classifications of pathogenicity in ALK (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-05-13). No gnomAD frequency available for this variant; Associated with neuroblastoma, susceptibility to, 3.

What condition is associated with ALK p.Ser895fs (c.2682dup)?

ALK p.Ser895fs (c.2682dup) is associated with neuroblastoma, susceptibility to, 3, hereditary neoplastic syndrome (ClinVar).

How common is ALK p.Ser895fs (c.2682dup) in the general population?

ALK p.Ser895fs (c.2682dup) is no gnomAD frequency available for this variant (gnomAD).

ALK p.Ser895fs

c.2682dup · rs1664103646 · VCV861509

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 16 of 29
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	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.Ser895fs
Coding: c.2682dup
MANE Select: NM_004304
dbSNP: rs1664103646
Type: Duplication
Location: chr2:29229016 (GRCh38)
Gene constraint: LOEUF 0.562 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.26 · 79 PDB
Residue 895: an α-helix

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 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
ALK p.Tyr406_Ile407insArgValAlaLeuGluTyr Uncertain significance ★★ same condition
ALK c.2632+11dup Benign/Likely benign ★★ 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-ser895fs (accessed [today's date]).

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