Is ALK p.Leu80= (c.238C>T) pathogenic?

ALK p.Leu80= (c.238C>T) is classified Likely benign in ALK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-28). Absent from gnomAD v4.1; Associated with neuroblastoma, susceptibility to, 3.

What condition is associated with ALK p.Leu80= (c.238C>T)?

ALK p.Leu80= (c.238C>T) is associated with neuroblastoma, susceptibility to, 3, hereditary neoplastic syndrome (ClinVar).

How common is ALK p.Leu80= (c.238C>T) in the general population?

ALK p.Leu80= (c.238C>T) is absent from gnomAD v4.1 (gnomAD).

ALK p.Leu80=

c.238C>T · rs2148443647 · VCV1665804

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.03	GERP -2.4
Overall
CADD	2.325	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ALK
Protein: p.Leu80=
Coding: c.238C>T
MANE Select: NM_004304
dbSNP: rs2148443647
Type: single nucleotide variant
Location: chr2:29920422 (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

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-leu80 (accessed [today's date]).

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