JAK1 p.Arg93=
c.279C>T · rs749516327 · VCV3023216
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.01%, amr)
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 0.61 | GERP 1.4 |
| Overall | ||
| CADD | 7.219 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.01%
Admixed American · 6/60,000 alleles
Filtering AF
0.00428%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00295%
Overall
0.000558%
9/1,613,894 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.01% | 10,000 |
| European (non-Finnish) | 0.000254% | 393,317 |
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.Arg93=
- Coding
- c.279C>T
- MANE Select
- NM_002227
- dbSNP
- rs749516327
- Type
- single nucleotide variant
- Location
- chr1:64879075 (GRCh38)
- Gene constraint
- LOEUF 0.168 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 85.68 · 52 PDB
- Residue 93
- the ferm domain
Similar variants
- JAK1 p.Arg93Cys Uncertain significance ★ ⚠ same residue
- JAK1 p.Arg93His Uncertain significance ★ ⚠ same residue
- JAK1 p.Arg93Leu Uncertain significance ★ ⚠ same residue
- JAK1 p.Arg1113Cys Uncertain significance ★★ ⚠ same type
- JAK1 p.Arg1113His Uncertain significance ★★ ⚠ same type
- JAK1 p.Arg219Gln Uncertain significance ★★ ⚠ same type
- JAK1 p.Arg360Trp Uncertain significance ★★ ⚠ same type
- JAK1 p.Arg454Trp 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-arg93 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown