Is ALK c.*111C>T pathogenic?

ALK c.111C>T is classified Benign in ALK (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-06-23). Common (popmax 5.68%, afr) — too common for a highly-penetrant pathogenic allele; Associated with neuroblastoma, susceptibility to, 3.

What condition is associated with ALK c.*111C>T?

ALK c.*111C>T is associated with neuroblastoma, susceptibility to, 3 (ClinVar).

ALK c.*111C>T

Q: How common is ALK c.*111C>T in the general population?

ALK c.*111C>T is common (popmax 5.68%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs74669215 · VCV335680

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 5.68%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

neuroblastoma, susceptibility to, 3

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 9.8	GERP 1.3, phastCons 1
Non-coding constraint	Z 0.71	1 kb window · o/e 0.93 · regional · uncalibrated
Overall
CADD	17.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.68% African / African-American · 3,791/66,762 alleles

Filtering AF 5.53% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.47%

Overall 0.348% 4,271/1,226,316 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.68%	18
Admixed American	0.415%	241
Remaining individualsnot grpmax-eligible	0.398%	251
Middle Eastern	0.239%	418
South Asian	0.00904%	11,065
European (non-Finnish)	0.0067%	14,923

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
Coding: c.*111C>T
MANE Select: NM_004304
dbSNP: rs74669215
Type: single nucleotide variant
Location: chr2:29193113 (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

neuroblastoma, susceptibility to, 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-c-star-111c-t (accessed [today's date]).

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