JAK1 p.Arg219=
c.657A>T · rs2101116455 · VCV1620103
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.57e-05%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.83 | GERP 1.7, phastCons 0.014 |
| Overall | ||
| CADD | 9.066 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.57e-05%
European (non-Finnish) · 1/1,167,316 alleles
Overall
6.93e-05%
1/1,443,048 alleles · very rare
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
- JAK1
- Protein
- p.Arg219=
- Coding
- c.657A>T
- MANE Select
- NM_002227
- dbSNP
- rs2101116455
- Type
- single nucleotide variant
- Location
- chr1:64867199 (GRCh38)
- Gene constraint
- LOEUF 0.168 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 85.68 · 52 PDB
- Residue 219
- the ferm domain; an α-helix
Similar variants
- JAK1 p.Arg219Gln Uncertain significance ★★ ⚠ same residue
- JAK1 p.Arg1113Cys Uncertain significance ★★ ⚠ same type
- JAK1 p.Arg1113His Uncertain significance ★★ ⚠ same type
- JAK1 p.Arg360Trp Uncertain significance ★★ ⚠ same type
- JAK1 p.Arg454Trp Uncertain significance ★★ ⚠ same type
- JAK1 p.Arg49Trp Uncertain significance ★★ ⚠ same type
- JAK1 p.Arg514Cys Uncertain significance ★★ ⚠ same type
- JAK1 p.Arg809Gln Uncertain significance ★★ ⚠ same type
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/jak1-p-arg219 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown