Is ALK p.Ala210= (c.630C>G) pathogenic?

ALK p.Ala210= (c.630C>G) is classified Conflicting classifications of pathogenicity in ALK (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-03). Very rare (popmax 8.47e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with ALK p.Ala210= (c.630C>G)?

ALK p.Ala210= (c.630C>G) is associated with hereditary neoplastic syndrome, neuroblastoma, susceptibility to, 3 (ClinVar).

How common is ALK p.Ala210= (c.630C>G) in the general population?

ALK p.Ala210= (c.630C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

ALK p.Ala210=

c.630C>G · rs1337002578 · VCV1097267

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 2.5	GERP 0.86, phastCons 1
Overall
CADD	11.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,040 alleles

Overall 0.000657% 1/152,256 alleles · very rare

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.Ala210=
Coding: c.630C>G
MANE Select: NM_004304
dbSNP: rs1337002578
Type: single nucleotide variant
Location: chr2:29920030 (GRCh38)
Gene constraint: LOEUF 0.562 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.26 · 79 PDB

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.Ala210Pro Uncertain significance ★ ⚠ same residue
ALK p.Ala210Ser Uncertain significance ★ same residue
ALK p.Ala210Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
ALK p.Ala210Val Uncertain significance ★ ⚠ same residue
ALK p.Ala210Leu 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

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-ala210 (accessed [today's date]).

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