Is ALK p.Ala624= (c.1872T>C) pathogenic?

ALK p.Ala624= (c.1872T>C) is classified Likely benign in ALK (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-20). Absent from gnomAD v4.1; Associated with neuroblastoma, susceptibility to, 3.

What condition is associated with ALK p.Ala624= (c.1872T>C)?

ALK p.Ala624= (c.1872T>C) is associated with neuroblastoma, susceptibility to, 3 (ClinVar).

How common is ALK p.Ala624= (c.1872T>C) in the general population?

ALK p.Ala624= (c.1872T>C) is absent from gnomAD v4.1 (gnomAD).

ALK p.Ala624=

c.1872T>C · rs1573183882 · VCV758515

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -0.21	GERP -4.1, phastCons 0.009
Overall
CADD	5.114	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ALK
Protein: p.Ala624=
Coding: c.1872T>C
MANE Select: NM_004304
dbSNP: rs1573183882
Type: single nucleotide variant
Location: chr2:29275442 (GRCh38)
Gene constraint: LOEUF 0.562 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.26 · 79 PDB
Residue 624: the mam 2 domain

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.Ala624Val Uncertain significance ★★ ⚠ same residue
ALK p.Ala624Pro Uncertain significance ★ ⚠ same residue
ALK p.Ala624Gly 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-ala624 (accessed [today's date]).

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