Is STAT4 p.Thr54= (c.162G>A) pathogenic?

STAT4 p.Thr54= (c.162G>A) is classified Likely benign in STAT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-06). Very rare (popmax 0.00121%, sas).

How common is STAT4 p.Thr54= (c.162G>A) in the general population?

STAT4 p.Thr54= (c.162G>A) is very rare (popmax 0.00121%, sas) (gnomAD).

STAT4 p.Thr54=

c.162G>A · rs867270053 · VCV757704

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00121%, sas)

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 -0.42	GERP -3.6, phastCons 0.17
Overall
CADD	7.251	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00121% South Asian · 1/82,446 alleles

Filtering AF 0.000296% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000214%

Overall 0.000633% 9/1,421,150 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00121%	82,446
European (non-Finnish)	0.000689%	145,194

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.Thr54=
Coding: c.162G>A
MANE Select: NM_003151
dbSNP: rs867270053
Type: single nucleotide variant
Location: chr2:191146724 (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.Thr54Ala Uncertain significance ★ ⚠ same residue
STAT4 p.Thr54Met Conflicting classifications of pathogenicity ★ ⚠ 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

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-thr54 (accessed [today's date]).

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