Is ALK p.Pro1144= (c.3432C>T) pathogenic?

ALK p.Pro1144= (c.3432C>T) is classified Likely benign in ALK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-05). Ultra-rare (popmax 0.0174%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with ALK p.Pro1144= (c.3432C>T)?

ALK p.Pro1144= (c.3432C>T) is associated with hereditary neoplastic syndrome, neuroblastoma, susceptibility to, 3 (ClinVar).

How common is ALK p.Pro1144= (c.3432C>T) in the general population?

ALK p.Pro1144= (c.3432C>T) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

ALK p.Pro1144=

c.3432C>T · rs148284008 · VCV470829

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -0.36, phastCons 1
Overall
CADD	9.155	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0174% African / African-American · 13/74,884 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00813%

Overall 0.000867% 14/1,614,008 alleles · ultra-rare exomes 8/1,461,886 · genomes 6/152,122 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0174%	5,760
European (non-Finnish)	8.47e-05%	1,180,036

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ALK
Protein: p.Pro1144=
Coding: c.3432C>T
MANE Select: NM_004304
dbSNP: rs148284008
Type: single nucleotide variant
Location: chr2:29222535 (GRCh38)
Gene constraint: LOEUF 0.562 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.26 · 79 PDB
Residue 1144: the protein kinase domain

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.Pro1144Leu Uncertain significance ★★ ⚠ same residue
ALK p.Pro1144Ser Uncertain significance ★★ ⚠ same residue
ALK p.Pro1144Arg 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-pro1144 (accessed [today's date]).

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