Is STAT4 p.His32Gln (c.96T>G) pathogenic?

STAT4 p.His32Gln (c.96T>G) is classified Uncertain significance in STAT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-08). AlphaMissense: likely benign (0.2334); Very rare (popmax 0.00167%, amr).

How common is STAT4 p.His32Gln (c.96T>G) in the general population?

STAT4 p.His32Gln (c.96T>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about STAT4 p.His32Gln (c.96T>G)?

AlphaMissense predicts likely benign (score 0.2334) — an in-silico prediction, not a clinical call.

STAT4 p.His32Gln

c.96T>G · rs766134008 · VCV2110013

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2334 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2334	likely benign
REVEL	0.107	moderately benign-leaning
SaProt	LLR -4.78	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 1	GERP -3.9, phastCons 0.99
Regional constraint	o/e 0.77	unconstrained · MANE · 114 kb · p 8.5e-09 · regional, not allelic
Overall
CADD	10.11	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,002 alleles

Overall 0.000124% 2/1,613,952 alleles · very rare exomes 2/1,461,602 · genomes 0/152,350 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,002
European (non-Finnish)	8.48e-05%	1,179,844

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.His32Gln
Coding: c.96T>G
MANE Select: NM_003151
dbSNP: rs766134008
Type: single nucleotide variant
Location: chr2:191148108 (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

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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
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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-his32gln (accessed [today's date]).

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