Is ALK p.Gln1064= (c.3192G>A) pathogenic?

ALK p.Gln1064= (c.3192G>A) is classified Likely benign in ALK (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-09-21). Rare (popmax 0.248%, mid); Associated with hereditary neoplastic syndrome.

What condition is associated with ALK p.Gln1064= (c.3192G>A)?

ALK p.Gln1064= (c.3192G>A) is associated with hereditary neoplastic syndrome, neuroblastoma, susceptibility to, 3 (ClinVar).

How common is ALK p.Gln1064= (c.3192G>A) in the general population?

ALK p.Gln1064= (c.3192G>A) is rare (popmax 0.248%, mid) (gnomAD).

ALK p.Gln1064=

c.3192G>A · rs868053991 · VCV470820

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.248%, mid)

Conditions

hereditary neoplastic syndrome

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 1.5	GERP 0.99, phastCons 1
Overall
CADD	10.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.248% Middle Eastern · 15/6,056 alleles

Filtering AF 0.153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.123%

Overall 0.00155% 25/1,613,988 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.248%	404
Remaining individualsnot grpmax-eligible	0.0064%	15,627
South Asian	0.0022%	45,532
Admixed American	0.00167%	60,024
African / African-American	0.00133%	75,034
European (non-Finnish)	0.000169%	590,016

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.Gln1064=
Coding: c.3192G>A
MANE Select: NM_004304
dbSNP: rs868053991
Type: single nucleotide variant
Location: chr2:29223509 (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

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

Also linked: neuroblastoma, susceptibility to, 3

Similar variants

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
ALK c.1546+4C>T 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-gln1064 (accessed [today's date]).

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