Is STAT4 p.Val123= (c.369C>G) pathogenic?

STAT4 p.Val123= (c.369C>G) is classified Likely benign in STAT4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-05-01). Very rare (popmax 0.00167%, amr).

How common is STAT4 p.Val123= (c.369C>G) in the general population?

STAT4 p.Val123= (c.369C>G) is very rare (popmax 0.00167%, amr) (gnomAD).

STAT4 p.Val123=

c.369C>G · rs948592364 · VCV1630930

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 0.65	GERP -3.8, phastCons 0.99
Overall
CADD	5.716	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,936 alleles

Overall 6.85e-05% 1/1,460,316 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.Val123=
Coding: c.369C>G
MANE Select: NM_003151
dbSNP: rs948592364
Type: single nucleotide variant
Location: chr2:191076230 (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.Val123Phe 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-val123 (accessed [today's date]).

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