SH2B3 p.Lys99=
c.297G>A · VCV4630695
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 9.13e-05%, nfe)
Conditions
1
Inborn genetic diseases
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 0.45 | GERP -2.4, phastCons 0.95 |
| Overall | ||
| CADD | 3.14 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
9.13e-05%
European (non-Finnish) · 1/1,094,720 alleles
Overall
7.86e-05%
1/1,272,328 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
- SH2B3
- Protein
- p.Lys99=
- Coding
- c.297G>A
- MANE Select
- NM_005475
- Type
- single nucleotide variant
- Location
- chr12:111418442 (GRCh38)
- Gene constraint
- LOEUF 1.35 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 63.45
- Residue 99
- the 'disordered' region
Similar variants
- SH2B3 p.Ala161Val Uncertain significance ★★ ⚠ same condition
- SH2B3 p.Ala174Thr Uncertain significance ★★ ⚠ same condition
- SH2B3 p.Ala300Thr Uncertain significance ★★ ⚠ same condition
- SH2B3 p.Arg221Met Uncertain significance ★★ ⚠ same condition
- SH2B3 p.Arg226Trp Uncertain significance ★★ ⚠ same condition
- SH2B3 p.Arg235Cys Uncertain significance ★★ ⚠ same condition
- SH2B3 p.Arg39Gln Uncertain significance ★★ ⚠ same condition
- SH2B3 p.Asp231Tyr Uncertain significance ★★ ⚠ same condition
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/sh2b3-p-lys99 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown