Is JAK2 p.Ser327Arg (c.979A>C) pathogenic?

JAK2 p.Ser327Arg (c.979A>C) is classified Uncertain significance in JAK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). AlphaMissense: likely pathogenic (0.7231); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with JAK2 p.Ser327Arg (c.979A>C)?

JAK2 p.Ser327Arg (c.979A>C) is associated with Inborn genetic diseases (ClinVar).

How common is JAK2 p.Ser327Arg (c.979A>C) in the general population?

JAK2 p.Ser327Arg (c.979A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about JAK2 p.Ser327Arg (c.979A>C)?

AlphaMissense predicts likely pathogenic (score 0.7231) — an in-silico prediction, not a clinical call.

JAK2 p.Ser327Arg

c.979A>C · rs2488977542 · VCV2287117

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7231 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

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	0.7231	likely pathogenic
REVEL	0.294	indeterminate
SaProt	LLR -7.88	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.4	GERP 1.6, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 105 kb · p 0.1 · regional, not allelic
Overall
CADD	25.1	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.Ser327Arg
Coding: c.979A>C
MANE Select: NM_004972
dbSNP: rs2488977542
Type: single nucleotide variant
Location: chr9:5055711 (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-ser327arg (accessed [today's date]).

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