Is JAK2 p.Leu1026Val (c.3076C>G) pathogenic?

JAK2 p.Leu1026Val (c.3076C>G) is classified Uncertain significance in JAK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-13). AlphaMissense: likely pathogenic (0.8108); Very rare (popmax 0.00017%, nfe); Associated with Inborn genetic diseases.

What condition is associated with JAK2 p.Leu1026Val (c.3076C>G)?

JAK2 p.Leu1026Val (c.3076C>G) is associated with Inborn genetic diseases (ClinVar).

How common is JAK2 p.Leu1026Val (c.3076C>G) in the general population?

JAK2 p.Leu1026Val (c.3076C>G) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about JAK2 p.Leu1026Val (c.3076C>G)?

AlphaMissense predicts likely pathogenic (score 0.8108) — an in-silico prediction, not a clinical call.

JAK2 p.Leu1026Val

c.3076C>G · rs774801005 · VCV2266456

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8108 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

⚠ 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
AlphaMissense	0.8108	likely pathogenic
REVEL	0.617	indeterminate
SaProt	LLR -10.46	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.5	GERP 1.9, phastCons 0.84
Regional constraint	o/e 1.04	unconstrained · MANE · 105 kb · p 0.1 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,177,562 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,610,360 alleles · very rare exomes 2/1,458,344 · genomes 0/152,016 · joint denominator

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.Leu1026Val
Coding: c.3076C>G
MANE Select: NM_004972
dbSNP: rs774801005
Type: single nucleotide variant
Location: chr9:5123020 (GRCh38)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-leu1026val (accessed [today's date]).

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