Is ALK p.Arg1530= (c.4590G>A) pathogenic?

ALK p.Arg1530= (c.4590G>A) is classified Likely benign in ALK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-11). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with ALK p.Arg1530= (c.4590G>A)?

ALK p.Arg1530= (c.4590G>A) is associated with hereditary neoplastic syndrome, neuroblastoma, susceptibility to, 3 (ClinVar).

How common is ALK p.Arg1530= (c.4590G>A) in the general population?

ALK p.Arg1530= (c.4590G>A) is absent from gnomAD v4.1 (gnomAD).

ALK p.Arg1530=

c.4590G>A · rs1668933679 · VCV1528867

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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
Pangolin	Δ0.51	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -1.4	GERP -4.5
Overall
CADD	0.452	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.Arg1530=
Coding: c.4590G>A
MANE Select: NM_004304
dbSNP: rs1668933679
Type: single nucleotide variant
Location: chr2:29193497 (GRCh38)
Gene constraint: LOEUF 0.562 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.26 · 79 PDB
Residue 1530: the 'disordered' region

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.Arg1530Ser Uncertain significance ★★ ⚠ same residue
ALK p.Arg1530Gly Uncertain significance ★ ⚠ same residue
ALK p.Arg1530Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
ALK p.Arg1530Met Uncertain significance ★ ⚠ same residue
ALK p.Arg1530Thr Uncertain significance ★ ⚠ same residue
ALK p.Arg1530fs Uncertain significance ★ same residue
ALK p.Arg1275Gln Pathogenic ★★ same condition
ALK c.1154+5G>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-arg1530 (accessed [today's date]).

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