Is ALK p.Gln1070= (c.3210G>A) pathogenic?

ALK p.Gln1070= (c.3210G>A) is classified Conflicting classifications of pathogenicity in ALK (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-11-30). Very rare (popmax 0.00246%, nfe); Associated with neuroblastoma, susceptibility to, 3.

What condition is associated with ALK p.Gln1070= (c.3210G>A)?

ALK p.Gln1070= (c.3210G>A) is associated with neuroblastoma, susceptibility to, 3, hereditary neoplastic syndrome (ClinVar).

How common is ALK p.Gln1070= (c.3210G>A) in the general population?

ALK p.Gln1070= (c.3210G>A) is very rare (popmax 0.00246%, nfe) (gnomAD).

ALK p.Gln1070=

c.3210G>A · rs138178848 · VCV538303

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00246%, 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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 1.9, phastCons 1
Overall
CADD	9.638	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00246% European (non-Finnish) · 29/1,180,048 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00186% 30/1,614,020 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00246%	40,691
South Asian	0.0011%	91,092

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
Protein: p.Gln1070=
Coding: c.3210G>A
MANE Select: NM_004304
dbSNP: rs138178848
Type: single nucleotide variant
Location: chr2:29223491 (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.Gln1070His Uncertain significance ★★ ⚠ same residue
ALK p.Arg1275Gln Pathogenic ★★ same condition
ALK c.1154+5G>A Uncertain significance ★★ same condition
ALK c.1155-3C>T Uncertain significance ★★ same condition
ALK c.1282+3A>G Uncertain significance ★★ same condition
ALK c.1414+1G>A Uncertain significance ★★ same condition
ALK c.1414+3G>A Uncertain significance ★★ same condition
ALK c.1415-3T>C 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-gln1070 (accessed [today's date]).

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