Is ALK p.Val1426Phe (c.4276G>T) pathogenic?

ALK p.Val1426Phe (c.4276G>T) is classified Uncertain significance in ALK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-10). AlphaMissense: likely benign (0.1553); Absent from gnomAD v4.1; Associated with neuroblastoma, susceptibility to, 3.

What condition is associated with ALK p.Val1426Phe (c.4276G>T)?

ALK p.Val1426Phe (c.4276G>T) is associated with neuroblastoma, susceptibility to, 3 (ClinVar).

How common is ALK p.Val1426Phe (c.4276G>T) in the general population?

ALK p.Val1426Phe (c.4276G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALK p.Val1426Phe (c.4276G>T)?

AlphaMissense predicts likely benign (score 0.1553) — an in-silico prediction, not a clinical call.

ALK p.Val1426Phe

c.4276G>T · rs1558604058 · VCV1357873

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1553 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

neuroblastoma, susceptibility to, 3

Computational evidence

Protein change
AlphaMissense	0.1553	likely benign
REVEL	0.43	indeterminate
SaProt	LLR -7.64	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.41	acceptor gain · deltas
Pangolin	Δ0.34	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.9	GERP 1.3, phastCons 0.99
Regional constraint	o/e 1.10	unconstrained · MANE · 4,393 bp · p 0.054 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Val1426Phe
Coding: c.4276G>T
MANE Select: NM_004304
dbSNP: rs1558604058
Type: single nucleotide variant
Location: chr2:29193811 (GRCh38)
Gene constraint: LOEUF 0.562 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.26 · 79 PDB
Residue 1426: the 'disordered' region

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.Val1426= Likely benign ★★ same residue
ALK p.Val1426Asp Uncertain significance ★ same residue
ALK p.Val1426Ile Uncertain significance ★ ⚠ same residue
ALK p.Val1426Ala 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

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-val1426phe (accessed [today's date]).

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