SH2B3 p.Phe275=
c.825T>C · VCV3795119
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00803%, afr)
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 -3.9 | GERP -1.6 |
| Overall | ||
| CADD | 5.624 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00803%
African / African-American · 6/74,728 alleles
Filtering AF
0.00348%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00239%
Overall
0.0005%
8/1,601,412 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00803% | 12,455 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,010 |
| European (non-Finnish) | 8.54e-05% | 1,171,044 |
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.Phe275=
- Coding
- c.825T>C
- MANE Select
- NM_005475
- Type
- single nucleotide variant
- Location
- chr12:111446845 (GRCh38)
- Gene constraint
- LOEUF 1.35 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 63.45
- Residue 275
- the ph domain; a UniProt-annotated variant site (found in a patient with isolated erythrocytosis; uncertain significance)
Similar variants
- SH2B3 p.Phe275Ile Uncertain significance ★ ⚠ same residue
- 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
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-phe275 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown