STAT2 p.Leu651=
c.1953C>T · VCV4917241
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0362%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.58 | GERP -1.6, phastCons 0.99 |
| Overall | ||
| CADD | 2.859 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0362%
South Asian · 33/91,078 alleles
Filtering AF
0.0265%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0231%
Overall
0.00254%
41/1,614,202 alleles · ultra-rare
exomes 41/1,461,890 · genomes 0/152,312 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0362% | 2,760 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,418 |
| European (non-Finnish) | 0.000169% | 590,019 |
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
- STAT2
- Protein
- p.Leu651=
- Coding
- c.1953C>T
- MANE Select
- NM_005419
- Type
- single nucleotide variant
- Location
- chr12:56346533 (GRCh38)
- Gene constraint
- LOEUF 0.497 · pLI 0.81 (gnomAD)
- Structure
- AlphaFold pLDDT 78.45 · 6 PDB
- Residue 651
- the sh2 domain
Similar variants
- STAT2 p.Arg667Ter Pathogenic/Likely pathogenic ★★ same type
- STAT2 p.Gln274Ter Pathogenic/Likely pathogenic ★★ same type
- STAT2 p.Ala219Thr Uncertain significance ★★ ⚠ same type
- STAT2 p.Ala302Thr Uncertain significance ★★ ⚠ same type
- STAT2 p.Arg300Cys Uncertain significance ★★ ⚠ same type
- STAT2 p.Arg330Gln Uncertain significance ★★ ⚠ same type
- STAT2 p.Arg409His Uncertain significance ★★ ⚠ same type
- STAT2 p.Arg510Gln 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/stat2-p-leu651 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown