STAT6 p.Ala321=
c.963G>A · VCV3772048
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00659%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.639 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.42 | donor gain · deltas |
| Constraint at this position | ||
| Conservation | phyloP -0.41 | GERP -4.2, phastCons 0.036 |
| Overall | ||
| CADD | 16.97 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00659%
South Asian · 6/91,086 alleles
Filtering AF
0.00286%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00195%
Overall
0.000868%
14/1,613,714 alleles · very rare
exomes 11/1,461,522 · genomes 3/152,192 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00659% | 15,181 |
| African / African-American | 0.00267% | 37,466 |
| European (non-Finnish) | 0.000509% | 196,650 |
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
- STAT6
- Protein
- p.Ala321=
- Coding
- c.963G>A
- MANE Select
- NM_003153
- Type
- single nucleotide variant
- Location
- chr12:57105189 (GRCh38)
- Gene constraint
- LOEUF 0.515 · pLI 0.56 (gnomAD)
- Structure
- AlphaFold pLDDT 77.44 · 7 PDB
- Residue 321
- a UniProt-annotated variant site (does not affect dna-binding transcription factor activity; does not affect stat6 phosphorylation); a turn
Similar variants
- STAT6 c.1001+10G>A Benign ★★ same type
- STAT6 c.1213-6C>T Benign ★★ same type
- STAT6 c.1744+9A>C Likely benign ★★ same type
- STAT6 p.Ser564= Benign/Likely benign ★★ same type
- STAT6 p.Val269Ile Benign ★★ same type
- STAT6 p.Asp419His Likely pathogenic ★ same type
- STAT6 p.Ala109Val Uncertain significance ★ ⚠ same type
- STAT6 p.Ala245Val 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/stat6-p-ala321 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown