Is ALK p.Glu570= (c.1710G>A) pathogenic?

ALK p.Glu570= (c.1710G>A) is classified Likely benign in ALK (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-09-10). Ultra-rare (popmax 0.099%, mid); Associated with neuroblastoma, susceptibility to, 3.

What condition is associated with ALK p.Glu570= (c.1710G>A)?

ALK p.Glu570= (c.1710G>A) is associated with neuroblastoma, susceptibility to, 3, hereditary neoplastic syndrome (ClinVar).

How common is ALK p.Glu570= (c.1710G>A) in the general population?

ALK p.Glu570= (c.1710G>A) is ultra-rare (popmax 0.099%, mid) (gnomAD).

ALK p.Glu570=

c.1710G>A · rs751328130 · VCV538302

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.099%, mid)

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 1.4	GERP 0.25, phastCons 1
Overall
CADD	8.279	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.099% Middle Eastern · 6/6,062 alleles

Filtering AF 0.043% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0294%

Overall 0.000434% 7/1,614,218 alleles · ultra-rare exomes 7/1,461,882 · genomes 0/152,336 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.099%	1,010
Remaining individualsnot grpmax-eligible	0.0016%	62,512

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.Glu570=
Coding: c.1710G>A
MANE Select: NM_004304
dbSNP: rs751328130
Type: single nucleotide variant
Location: chr2:29296995 (GRCh38)
Gene constraint: LOEUF 0.562 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.26 · 79 PDB
Residue 570: 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

Also linked: hereditary neoplastic syndrome

Similar variants

ALK p.Glu570Asp Uncertain significance ★★ ⚠ same residue
ALK p.Glu570Ala Uncertain significance ★ ⚠ same residue
ALK p.Glu570Gln Uncertain significance ★ ⚠ same residue
ALK p.Glu570Lys 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

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-glu570 (accessed [today's date]).

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