Is STAT4 p.His532= (c.1596C>T) pathogenic?

STAT4 p.His532= (c.1596C>T) is classified Likely benign in STAT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-22). Rare (popmax 0.121%, afr).

How common is STAT4 p.His532= (c.1596C>T) in the general population?

STAT4 p.His532= (c.1596C>T) is rare (popmax 0.121%, afr) (gnomAD).

STAT4 p.His532=

c.1596C>T · rs147850919 · VCV722698

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.121%, 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 0.35	GERP -1.4, phastCons 0.91
Overall
CADD	4.543	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.121% African / African-American · 91/75,004 alleles

Filtering AF 0.101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0937%

Overall 0.00638% 103/1,613,744 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.121%	824
Admixed American	0.01%	10,001
Remaining individualsnot grpmax-eligible	0.0064%	15,624
East Asian	0.00446%	22,433

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.His532=
Coding: c.1596C>T
MANE Select: NM_003151
dbSNP: rs147850919
Type: single nucleotide variant
Location: chr2:191034572 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.93 (gnomAD)
Structure: AlphaFold pLDDT 86.87

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

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-his532 (accessed [today's date]).

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