STAT4 p.Thr446=
c.1338C>A · rs144421302 · VCV715628
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.476%, nfe)
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 2.6 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 11.14 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.476%
European (non-Finnish) · 5,620/1,179,824 alleles
Filtering AF
0.466%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.462%
Overall
0.384%
6,197/1,613,936 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.476% | 210 |
| Finnishnot grpmax-eligible | 0.412% | 243 |
| Remaining individualsnot grpmax-eligible | 0.35% | 285 |
| African / African-American | 0.0746% | 1,340 |
| Admixed American | 0.0566% | 1,765 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0101% | 9,869 |
| South Asian | 0.0011% | 91,066 |
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
- STAT4
- Protein
- p.Thr446=
- Coding
- c.1338C>A
- MANE Select
- NM_003151
- dbSNP
- rs144421302
- Type
- single nucleotide variant
- Location
- chr2:191039295 (GRCh38)
- Gene constraint
- LOEUF 0.503 · pLI 0.93 (gnomAD)
- Structure
- AlphaFold pLDDT 86.87
Similar variants
- STAT4 p.Thr446Ile Conflicting classifications of pathogenicity ★ same residue
- STAT4 p.Ala245Thr Uncertain significance ★★ ⚠ same type
- STAT4 p.Arg241Gln Uncertain significance ★★ ⚠ same type
- STAT4 p.Arg70Leu Uncertain significance ★★ ⚠ same type
- STAT4 p.Arg87Lys Uncertain significance ★★ ⚠ same type
- STAT4 p.Asp513Val Uncertain significance ★★ ⚠ same type
- STAT4 p.Cys323Arg Uncertain significance ★★ ⚠ same type
- STAT4 p.Gln243Lys 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/stat4-p-thr446 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown