STAT4 p.Arg174=
c.522G>A · rs1220885174 · VCV795935
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00508%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.44 | donor loss, 1 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.62 | GERP -3.5, phastCons 0.021 |
| Overall | ||
| CADD | 5.805 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00508%
Admixed American · 3/59,072 alleles
Filtering AF
0.00135%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000674%
Overall
0.000435%
7/1,609,540 alleles · very rare
exomes 6/1,457,422 · genomes 1/152,118 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00508% | 19,691 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,154 |
| European (non-Finnish) | 0.00017% | 589,227 |
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.Arg174=
- Coding
- c.522G>A
- MANE Select
- NM_003151
- dbSNP
- rs1220885174
- Type
- single nucleotide variant
- Location
- chr2:191069715 (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-arg174 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown