Is JAK2 p.Leu352= (c.1054C>T) pathogenic?

JAK2 p.Leu352= (c.1054C>T) is classified Uncertain significance in JAK2 (ClinVar, Single submitter, 1 submitter). Very rare (popmax 0.00221%, sas); Associated with thrombocythemia 3.

What condition is associated with JAK2 p.Leu352= (c.1054C>T)?

JAK2 p.Leu352= (c.1054C>T) is associated with thrombocythemia 3 (ClinVar).

How common is JAK2 p.Leu352= (c.1054C>T) in the general population?

JAK2 p.Leu352= (c.1054C>T) is very rare (popmax 0.00221%, sas) (gnomAD).

How is Familial thrombocytosis inherited?

Typically Autosomal dominant, X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

JAK2 p.Leu352=

c.1054C>T · rs763096519 · VCV2585137

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00221%, sas)

Conditions

thrombocythemia 3

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.3	GERP -1.5, phastCons 1
Overall
CADD	13.59	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00221% South Asian · 2/90,670 alleles

Filtering AF 0.000366% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000186% 3/1,609,386 alleles · very rare exomes 3/1,457,308 · genomes 0/152,078 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00221%	45,335
Remaining individualsnot grpmax-eligible	0.00161%	62,264

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: JAK2
Protein: p.Leu352=
Coding: c.1054C>T
MANE Select: NM_004972
dbSNP: rs763096519
Type: single nucleotide variant
Location: chr9:5055786 (GRCh38)

Full JAK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

thrombocythemia 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial thrombocytosis (Orphanet):

Inheritance: Autosomal dominant, X-linked recessive
Onset: Childhood
Prevalence: <1 / 1 000 000 (Worldwide)

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/jak2-p-leu352 (accessed [today's date]).

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