STAT6 p.Ala422=
c.1266C>A · rs144530864 · VCV724684
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.026 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.9 | GERP -2.5, phastCons 1 |
| Overall | ||
| CADD | 11.09 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,058 alleles
Filtering AF
0.0228%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0218%
Overall
0.0191%
308/1,612,976 alleles · ultra-rare
exomes 293/1,461,332 · genomes 15/151,644 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,029 |
| European (non-Finnish) | 0.0252% | 3,972 |
| Remaining individualsnot grpmax-eligible | 0.00641% | 15,610 |
| African / African-American | 0.00535% | 18,702 |
| Admixed American | 0.00167% | 59,916 |
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.Ala422=
- Coding
- c.1266C>A
- MANE Select
- NM_003153
- dbSNP
- rs144530864
- Type
- single nucleotide variant
- Location
- chr12:57102868 (GRCh38)
- Gene constraint
- LOEUF 0.515 · pLI 0.56 (gnomAD)
- Structure
- AlphaFold pLDDT 77.44 · 7 PDB
- Residue 422
- an α-helix
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-ala422 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown