Is ALK p.Asn563= (c.1689C>T) pathogenic?

ALK p.Asn563= (c.1689C>T) is classified Benign/Likely benign in ALK (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-31). Rare (popmax 0.789%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with ALK p.Asn563= (c.1689C>T)?

ALK p.Asn563= (c.1689C>T) is associated with hereditary neoplastic syndrome, neuroblastoma, susceptibility to, 3 (ClinVar).

How common is ALK p.Asn563= (c.1689C>T) in the general population?

ALK p.Asn563= (c.1689C>T) is rare (popmax 0.789%, sas) (gnomAD).

ALK p.Asn563=

c.1689C>T · rs565743321 · VCV412925

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.789%, sas)

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 -6.8	GERP -4.4
Overall
CADD	1.635	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.789% South Asian · 719/91,080 alleles

Filtering AF 0.742% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.723%

Overall 0.0516% 833/1,614,160 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.789%	127
Remaining individualsnot grpmax-eligible	0.072%	1,389
Middle Eastern	0.066%	1,516
Admixed American	0.01%	10,001
European (non-Finnish)	0.00449%	22,265
East Asian	0.00446%	22,442
African / African-American	0.004%	25,018
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606

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.Asn563=
Coding: c.1689C>T
MANE Select: NM_004304
dbSNP: rs565743321
Type: single nucleotide variant
Location: chr2:29297016 (GRCh38)
Gene constraint: LOEUF 0.562 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.26 · 79 PDB
Residue 563: the mam 2 domain

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.Asn563Ile Uncertain significance ★ ⚠ same residue
ALK p.Asn563Lys Conflicting classifications of pathogenicity ★ ⚠ 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
ALK c.1414+3G>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-asn563 (accessed [today's date]).

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