Is STAT4 p.Ile115Val (c.343A>G) pathogenic?

STAT4 p.Ile115Val (c.343A>G) is classified Likely benign in STAT4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-05-01). AlphaMissense: ambiguous (0.4264); Rare (popmax 0.975%, afr).

How common is STAT4 p.Ile115Val (c.343A>G) in the general population?

STAT4 p.Ile115Val (c.343A>G) is rare (popmax 0.975%, afr) (gnomAD).

What do computational predictors say about STAT4 p.Ile115Val (c.343A>G)?

AlphaMissense predicts ambiguous (score 0.4264) — an in-silico prediction, not a clinical call.

STAT4 p.Ile115Val

c.343A>G · rs3024839 · VCV741427

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4264 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.975%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4264	ambiguous
REVEL	0.176	moderately benign-leaning
SaProt	LLR -8.88	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 114 kb · p 8.5e-09 · regional, not allelic
Overall
CADD	24.1	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 0.975% African / African-American · 731/74,992 alleles

Filtering AF 0.916% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.893%

Overall 0.0509% 821/1,613,904 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.975%	103
Remaining individualsnot grpmax-eligible	0.08%	1,250
Admixed American	0.0483%	2,069
Middle Eastern	0.033%	3,030
South Asian	0.0022%	45,541
European (non-Finnish)	0.000593%	168,557

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.Ile115Val
Coding: c.343A>G
MANE Select: NM_003151
dbSNP: rs3024839
Type: single nucleotide variant
Location: chr2:191076256 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.93 (gnomAD)
Structure: AlphaFold pLDDT 86.87
Residue 115: a UniProt-annotated variant site (in)

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-ile115val (accessed [today's date]).

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