Is ALK p.Thr697= (c.2091C>A) pathogenic?

ALK p.Thr697= (c.2091C>A) is classified Likely benign in ALK (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-29). Very rare (popmax 0.00223%, eas); Associated with neuroblastoma, susceptibility to, 3.

What condition is associated with ALK p.Thr697= (c.2091C>A)?

ALK p.Thr697= (c.2091C>A) is associated with neuroblastoma, susceptibility to, 3 (ClinVar).

How common is ALK p.Thr697= (c.2091C>A) in the general population?

ALK p.Thr697= (c.2091C>A) is very rare (popmax 0.00223%, eas) (gnomAD).

ALK p.Thr697=

c.2091C>A · rs1252650401 · VCV1589575

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 -4.3	GERP -4.7
Overall
CADD	0.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,880 alleles

Overall 0.000124% 2/1,614,098 alleles · very rare exomes 2/1,461,758 · genomes 0/152,340 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,880
European (non-Finnish)	8.47e-05%	1,180,002

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.Thr697=
Coding: c.2091C>A
MANE Select: NM_004304
dbSNP: rs1252650401
Type: single nucleotide variant
Location: chr2:29251218 (GRCh38)
Gene constraint: LOEUF 0.562 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.26 · 79 PDB
Residue 697: 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

Similar variants

ALK p.Thr697Asn Uncertain significance ★ ⚠ same residue
ALK p.Thr697Ser Uncertain significance ★ ⚠ same residue
ALK p.Thr697Ala 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

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-thr697 (accessed [today's date]).

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