STAT4 p.Ser133=
c.399T>C · rs997364411 · VCV1583710
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0183%, amr)
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 | GERP -0.69, phastCons 1 |
| Overall | ||
| CADD | 9.004 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0183%
Admixed American · 11/59,994 alleles
Filtering AF
0.0102%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00785%
Overall
0.000991%
16/1,613,840 alleles · ultra-rare
exomes 6/1,461,678 · genomes 10/152,162 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0183% | 5,454 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,827 |
| European (non-Finnish) | 0.00017% | 589,964 |
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.Ser133=
- Coding
- c.399T>C
- MANE Select
- NM_003151
- dbSNP
- rs997364411
- Type
- single nucleotide variant
- Location
- chr2:191073164 (GRCh38)
- Gene constraint
- LOEUF 0.503 · pLI 0.93 (gnomAD)
- Structure
- AlphaFold pLDDT 86.87
Similar variants
- 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
- STAT4 p.Gly393Ala 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-ser133 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown