Is STAT4 p.Arg584= (c.1750C>A) pathogenic?

STAT4 p.Arg584= (c.1750C>A) is classified Likely benign in STAT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-15). Very rare (popmax 8.48e-05%, nfe).

How common is STAT4 p.Arg584= (c.1750C>A) in the general population?

STAT4 p.Arg584= (c.1750C>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

STAT4 p.Arg584=

c.1750C>A · rs3024933 · VCV1634817

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.28	acceptor loss · deltas
Pangolin	Δ0.32	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.3	GERP 0.96, phastCons 1
Overall
CADD	4.548	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,920 alleles

Overall 6.84e-05% 1/1,461,580 alleles · very rare

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.Arg584=
Coding: c.1750C>A
MANE Select: NM_003151
dbSNP: rs3024933
Type: single nucleotide variant
Location: chr2:191033592 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.93 (gnomAD)
Structure: AlphaFold pLDDT 86.87
Residue 584: the sh2 domain; a UniProt-annotated variant site (in)

Full STAT4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

STAT4 p.Arg584Trp 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-arg584 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown