Is ALK p.Tyr826= (c.2478C>T) pathogenic?

ALK p.Tyr826= (c.2478C>T) is classified Benign/Likely benign in ALK (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-05-01). Ultra-rare (popmax 0.0251%, nfe); Associated with neuroblastoma, susceptibility to, 3.

What condition is associated with ALK p.Tyr826= (c.2478C>T)?

ALK p.Tyr826= (c.2478C>T) is associated with neuroblastoma, susceptibility to, 3, hereditary neoplastic syndrome (ClinVar).

How common is ALK p.Tyr826= (c.2478C>T) in the general population?

ALK p.Tyr826= (c.2478C>T) is ultra-rare (popmax 0.0251%, nfe) (gnomAD).

ALK p.Tyr826=

c.2478C>T · rs142126984 · VCV239806

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0251%, nfe)

Conditions

neuroblastoma, susceptibility to, 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.58	GERP -3.4, phastCons 0.001
Overall
CADD	12.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0251% European (non-Finnish) · 296/1,180,034 alleles

Filtering AF 0.0227% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0217%

Overall 0.0198% 319/1,614,144 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0251%	3,987
Middle Eastern	0.0165%	6,060
Admixed American	0.01%	10,002
Remaining individualsnot grpmax-eligible	0.008%	12,502
African / African-American	0.008%	12,506
South Asian	0.00329%	30,359
Finnishnot grpmax-eligible	0.00312%	32,008

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.Tyr826=
Coding: c.2478C>T
MANE Select: NM_004304
dbSNP: rs142126984
Type: single nucleotide variant
Location: chr2:29233574 (GRCh38)
Gene constraint: LOEUF 0.562 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.26 · 79 PDB
Residue 826: a β-strand

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.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
ALK c.1415-3T>C Uncertain significance ★★ same condition
ALK c.1546+4C>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-tyr826 (accessed [today's date]).

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