Is ALK p.Lys1612= (c.4836G>A) pathogenic?

ALK p.Lys1612= (c.4836G>A) is classified Benign/Likely benign in ALK (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Low-frequency (popmax 1.23%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with ALK p.Lys1612= (c.4836G>A)?

ALK p.Lys1612= (c.4836G>A) is associated with hereditary neoplastic syndrome, neuroblastoma, susceptibility to, 3 (ClinVar).

How common is ALK p.Lys1612= (c.4836G>A) in the general population?

ALK p.Lys1612= (c.4836G>A) is low-frequency (popmax 1.23%, afr) (gnomAD).

ALK p.Lys1612=

c.4836G>A · rs78174819 · VCV239846

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.23%, afr)

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 1.2	GERP 1.3, phastCons 0.99
Overall
CADD	7.117	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.23% African / African-American · 920/75,034 alleles

Filtering AF 1.16% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.13%

Overall 0.083% 1,340/1,614,136 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.23%	82
Remaining individualsnot grpmax-eligible	0.11%	906
Admixed American	0.08%	1,250
Middle Eastern	0.033%	3,030
European (non-Finnish)	0.0245%	4,083
South Asian	0.0132%	7,589

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.Lys1612=
Coding: c.4836G>A
MANE Select: NM_004304
dbSNP: rs78174819
Type: single nucleotide variant
Location: chr2:29193251 (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.Lys1612Asn Uncertain significance ★ ⚠ same residue
ALK p.Lys1612Gln 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
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-lys1612 (accessed [today's date]).

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