Is JAK2 p.Ile237Phe (c.709A>T) pathogenic?

JAK2 p.Ile237Phe (c.709A>T) is classified Uncertain significance in JAK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-27). AlphaMissense: likely pathogenic (0.7824); Very rare (popmax 0.00432%, nfe); Associated with Inborn genetic diseases.

What condition is associated with JAK2 p.Ile237Phe (c.709A>T)?

JAK2 p.Ile237Phe (c.709A>T) is associated with Inborn genetic diseases (ClinVar).

How common is JAK2 p.Ile237Phe (c.709A>T) in the general population?

JAK2 p.Ile237Phe (c.709A>T) is very rare (popmax 0.00432%, nfe) (gnomAD).

What do computational predictors say about JAK2 p.Ile237Phe (c.709A>T)?

AlphaMissense predicts likely pathogenic (score 0.7824) — an in-silico prediction, not a clinical call.

JAK2 p.Ile237Phe

c.709A>T · VCV3531249

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7824 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00432%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

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	0.7824	likely pathogenic
REVEL	0.22	benign-leaning
SaProt	LLR -8.93	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 105 kb · p 0.1 · regional, not allelic
Overall
CADD	25.6	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

Grpmax group 0.00432% European (non-Finnish) · 51/1,179,404 alleles

Filtering AF 0.00334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00302%

Overall 0.00341% 55/1,613,242 alleles · very rare exomes 51/1,461,160 · genomes 4/152,082 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00432%	23,126
Remaining individualsnot grpmax-eligible	0.0032%	31,225
African / African-American	0.00267%	37,453

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.Ile237Phe
Coding: c.709A>T
MANE Select: NM_004972
Type: single nucleotide variant
Location: chr9:5054657 (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-ile237phe (accessed [today's date]).

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