Is JAK2 p.Cys787Ser (c.2359T>A) pathogenic?

JAK2 p.Cys787Ser (c.2359T>A) is classified Uncertain significance in JAK2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-12). AlphaMissense: likely pathogenic (0.8176); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with JAK2 p.Cys787Ser (c.2359T>A)?

JAK2 p.Cys787Ser (c.2359T>A) is associated with Inborn genetic diseases (ClinVar).

How common is JAK2 p.Cys787Ser (c.2359T>A) in the general population?

JAK2 p.Cys787Ser (c.2359T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about JAK2 p.Cys787Ser (c.2359T>A)?

AlphaMissense predicts likely pathogenic (score 0.8176) — an in-silico prediction, not a clinical call.

JAK2 p.Cys787Ser

c.2359T>A · rs747928693 · VCV1957962

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8176 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8176	likely pathogenic
REVEL	0.882	moderately pathogenic-leaning
SaProt	LLR -9.68	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 105 kb · p 0.1 · regional, not allelic
Overall
CADD	27.7	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: JAK2
Protein: p.Cys787Ser
Coding: c.2359T>A
MANE Select: NM_007179 · reported on NM_004972
dbSNP: rs747928693
Type: single nucleotide variant
Location: chr9:5080608 (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-cys787ser (accessed [today's date]).

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