Is ALK p.Ala55Val (c.164C>T) pathogenic?

ALK p.Ala55Val (c.164C>T) is classified Uncertain significance in ALK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-14). AlphaMissense: likely pathogenic (0.9261); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with ALK p.Ala55Val (c.164C>T)?

ALK p.Ala55Val (c.164C>T) is associated with hereditary neoplastic syndrome, neuroblastoma, susceptibility to, 3 (ClinVar).

How common is ALK p.Ala55Val (c.164C>T) in the general population?

ALK p.Ala55Val (c.164C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALK p.Ala55Val (c.164C>T)?

AlphaMissense predicts likely pathogenic (score 0.9261) — an in-silico prediction, not a clinical call.

ALK p.Ala55Val

c.164C>T · rs1217013970 · VCV1520805

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9261 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9261	likely pathogenic
REVEL	0.167	moderately benign-leaning
SaProt	LLR -5.95	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 1.8, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 670 kb · p 0.12 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

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.Ala55Val
Coding: c.164C>T
MANE Select: NM_004304
dbSNP: rs1217013970
Type: single nucleotide variant
Location: chr2:29920496 (GRCh38)
Gene constraint: LOEUF 0.562 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.26 · 79 PDB
Residue 55: the 'heparin-binding region' region

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.Ala55Ser Uncertain significance ★ ⚠ same residue
ALK p.Ala55= Likely benign ★ same residue
ALK p.Ala55Glu 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

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-ala55val (accessed [today's date]).

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