Is ALK p.Ala1200= (c.3600G>A) pathogenic?

ALK p.Ala1200= (c.3600G>A) is classified Benign/Likely benign in ALK (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-26). Rare (popmax 0.165%, mid); Associated with hereditary neoplastic syndrome.

What condition is associated with ALK p.Ala1200= (c.3600G>A)?

ALK p.Ala1200= (c.3600G>A) is associated with hereditary neoplastic syndrome, neuroblastoma, susceptibility to, 3 (ClinVar).

How common is ALK p.Ala1200= (c.3600G>A) in the general population?

ALK p.Ala1200= (c.3600G>A) is rare (popmax 0.165%, mid) (gnomAD).

ALK p.Ala1200=

c.3600G>A · rs56247462 · VCV239826

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.165%, 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 -20	GERP -3.7
Overall
CADD	0.005	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.165% Middle Eastern · 10/6,058 alleles

Filtering AF 0.0895% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0681%

Overall 0.0134% 217/1,613,912 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.165%	606
African / African-American	0.0613%	1,631
Admixed American	0.0417%	2,400
Remaining individualsnot grpmax-eligible	0.0256%	3,906
South Asian	0.011%	9,106
European (non-Finnish)	0.00924%	10,824
Finnishnot grpmax-eligible	0.00156%	64,036

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.Ala1200=
Coding: c.3600G>A
MANE Select: NM_004304
dbSNP: rs56247462
Type: single nucleotide variant
Location: chr2:29220751 (GRCh38)
Gene constraint: LOEUF 0.562 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.26 · 79 PDB
Residue 1200: 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.Ala1200Gly Uncertain significance ★★ ⚠ same residue
ALK p.Ala1200Thr Uncertain significance ★ ⚠ same residue
ALK p.Ala1200Val Conflicting classifications of pathogenicity ★ ⚠ 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

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-ala1200 (accessed [today's date]).

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