Is ALK p.Ala55Glu (c.164C>A) pathogenic?

ALK p.Ala55Glu (c.164C>A) is classified Uncertain significance in ALK (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-13). AlphaMissense: likely pathogenic (0.9901); Absent from gnomAD v4.1; Associated with familial isolated pituitary adenoma.

What condition is associated with ALK p.Ala55Glu (c.164C>A)?

ALK p.Ala55Glu (c.164C>A) is associated with familial isolated pituitary adenoma (ClinVar).

How common is ALK p.Ala55Glu (c.164C>A) in the general population?

ALK p.Ala55Glu (c.164C>A) is absent from gnomAD v4.1 (gnomAD).

How is Familial isolated pituitary adenoma inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ALK p.Ala55Glu (c.164C>A)?

AlphaMissense predicts likely pathogenic (score 0.9901) — an in-silico prediction, not a clinical call.

ALK p.Ala55Glu

c.164C>A · rs1217013970 · VCV620599

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9901 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial isolated pituitary adenoma

Computational evidence

Protein change
AlphaMissense	0.9901	likely pathogenic · top 9% in ALK
REVEL	0.229	benign-leaning
SaProt	LLR -5.80	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	29.6	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.Ala55Glu
Coding: c.164C>A
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

familial isolated pituitary adenoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial isolated pituitary adenoma (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood, Elderly, Infancy

Similar variants

ALK p.Ala55Val Uncertain significance ★★ ⚠ same residue
ALK p.Ala55Ser Uncertain significance ★ ⚠ same residue
ALK p.Ala55= Likely benign ★ same residue
ALK p.Asn398Ser Uncertain significance ★★ ⚠ same condition
ALK p.Leu506Pro Uncertain significance ★★ ⚠ same condition
ALK c.1283-5T>C Conflicting classifications of pathogenicity ★ same condition
ALK c.2633-3C>T Conflicting classifications of pathogenicity ★ same condition
ALK p.Ala528Thr Conflicting classifications of pathogenicity ★ ⚠ 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-ala55glu (accessed [today's date]).

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