Is ALK p.Val1019= (c.3057C>A) pathogenic?

ALK p.Val1019= (c.3057C>A) is classified Benign/Likely benign in ALK (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-06-01). Low-frequency (popmax 1.31%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with ALK p.Val1019= (c.3057C>A)?

ALK p.Val1019= (c.3057C>A) is associated with hereditary neoplastic syndrome, neuroblastoma, susceptibility to, 3 (ClinVar).

How common is ALK p.Val1019= (c.3057C>A) in the general population?

ALK p.Val1019= (c.3057C>A) is low-frequency (popmax 1.31%, sas) (gnomAD).

ALK p.Val1019=

c.3057C>A · rs138406372 · VCV335698

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.31%, 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 7.3	GERP 1.3, phastCons 1
Overall
CADD	5.064	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.31% South Asian · 1,191/91,088 alleles

Filtering AF 1.25% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.22%

Overall 0.129% 2,082/1,614,212 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.31%	76
Ashkenazi Jewishnot grpmax-eligible	1.21%	82
Middle Eastern	0.662%	151
Remaining individualsnot grpmax-eligible	0.216%	463
Admixed American	0.0466%	2,144
European (non-Finnish)	0.0276%	3,620
African / African-American	0.00266%	37,532
East Asian	0.00223%	44,886

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.Val1019=
Coding: c.3057C>A
MANE Select: NM_004304
dbSNP: rs138406372
Type: single nucleotide variant
Location: chr2:29226932 (GRCh38)
Gene constraint: LOEUF 0.562 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.26 · 79 PDB
Residue 1019: the 'egf-like' region; a β-strand; a disulfide bond

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.Val1019Phe Uncertain significance ★★ ⚠ same residue
ALK p.Val1019Ile 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-val1019 (accessed [today's date]).

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