Is ALK p.Glu1558Val (c.4673_4674delinsTC) pathogenic?

ALK p.Glu1558Val (c.46734674delinsTC) is classified Uncertain significance in ALK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-10). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with ALK p.Glu1558Val (c.4673_4674delinsTC)?

ALK p.Glu1558Val (c.4673_4674delinsTC) is associated with hereditary neoplastic syndrome, neuroblastoma, susceptibility to, 3 (ClinVar).

How common is ALK p.Glu1558Val (c.4673_4674delinsTC) in the general population?

ALK p.Glu1558Val (c.4673_4674delinsTC) is absent from gnomAD (gnomAD).

ALK p.Glu1558Val

c.4673_4674delinsTC · rs2148137555 · VCV1413932

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 · substitutions only
Constraint at this position
Conservation	phyloP -0.29	GERP -4.9, phastCons 0.26
Regional constraint	o/e 1.10	unconstrained · MANE · 4,393 bp · p 0.054 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ALK
Protein: p.Glu1558Val
Coding: c.4673_4674delinsTC
MANE Select: NM_004304
dbSNP: rs2148137555
Type: Indel
Location: chr2:29193413 (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.Glu1558Gly Uncertain significance ★★ ⚠ same residue
ALK p.Glu1558= Likely benign ★★ same residue
ALK p.Glu1558Asp Uncertain significance ★ ⚠ same residue
ALK p.Glu1558Gln Uncertain significance ★ ⚠ same residue
ALK p.Glu1558Lys Uncertain significance ★ ⚠ same residue
ALK c.3359+4_3359+6delinsGGT Uncertain significance ★★ same condition
ALK c.4165-6_4165-5delinsTA Uncertain significance ★★ same condition
ALK p.Glu1161Thr 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-glu1558val (accessed [today's date]).

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