STAT4 p.Arg643=
c.1927C>A · rs759048381 · VCV2911762
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.004%, afr)
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 5.8 | GERP 0.8, phastCons 1 |
| Overall | ||
| CADD | 9.465 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.004%
African / African-American · 3/74,922 alleles
Filtering AF
0.00267%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00236%
Overall
0.00279%
45/1,614,054 alleles · very rare
exomes 39/1,461,882 · genomes 6/152,172 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.004% | 24,974 |
| European (non-Finnish) | 0.00356% | 28,096 |
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.Arg643=
- Coding
- c.1927C>A
- MANE Select
- NM_003151
- dbSNP
- rs759048381
- Type
- single nucleotide variant
- Location
- chr2:191033075 (GRCh38)
- Gene constraint
- LOEUF 0.503 · pLI 0.93 (gnomAD)
- Structure
- AlphaFold pLDDT 86.87
- Residue 643
- the sh2 domain
Similar variants
- STAT4 p.Arg643Gln Uncertain significance ★ ⚠ 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-arg643 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown