Is STAT4 p.Arg240Gln (c.719G>A) pathogenic?

STAT4 p.Arg240Gln (c.719G>A) is classified Likely benign in STAT4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.0938); Rare (popmax 0.29%, nfe).

How common is STAT4 p.Arg240Gln (c.719G>A) in the general population?

STAT4 p.Arg240Gln (c.719G>A) is rare (popmax 0.29%, nfe) (gnomAD).

What do computational predictors say about STAT4 p.Arg240Gln (c.719G>A)?

AlphaMissense predicts likely benign (score 0.0938) — an in-silico prediction, not a clinical call.

STAT4 p.Arg240Gln

c.719G>A · rs61756200 · VCV1644768

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0938 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.29%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0938	likely benign
REVEL	0.214	benign-leaning
SaProt	LLR -8.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.1, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 114 kb · p 8.5e-09 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.29% European (non-Finnish) · 3,418/1,179,644 alleles

Filtering AF 0.282% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.278%

Overall 0.226% 3,652/1,613,314 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.29%	345
Remaining individualsnot grpmax-eligible	0.162%	619
Admixed American	0.122%	821
Middle Eastern	0.0663%	1,509
African / African-American	0.0414%	2,418
Ashkenazi Jewishnot grpmax-eligible	0.0203%	4,933
Finnishnot grpmax-eligible	0.0172%	5,819
East Asian	0.00893%	11,193
South Asian	0.0044%	22,747

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.Arg240Gln
Coding: c.719G>A
MANE Select: NM_003151
dbSNP: rs61756200
Type: single nucleotide variant
Location: chr2:191064870 (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.Arg240Trp 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-arg240gln (accessed [today's date]).

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