Is STAT4 p.Glu200Val (c.599A>T) pathogenic?

STAT4 p.Glu200Val (c.599A>T) is classified Uncertain significance in STAT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-15). AlphaMissense: likely benign (0.2098); Very rare (popmax 0.000509%, nfe).

How common is STAT4 p.Glu200Val (c.599A>T) in the general population?

STAT4 p.Glu200Val (c.599A>T) is very rare (popmax 0.000509%, nfe) (gnomAD).

What do computational predictors say about STAT4 p.Glu200Val (c.599A>T)?

AlphaMissense predicts likely benign (score 0.2098) — an in-silico prediction, not a clinical call.

STAT4 p.Glu200Val

c.599A>T · rs2470779371 · VCV1715188

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2098 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2098	likely benign
REVEL	0.19	benign-leaning
SaProt	LLR -8.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.88	donor gain · deltas
Pangolin	Δ0.63	gain · loss 0.21 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6.2	GERP 1.6, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 114 kb · p 8.5e-09 · regional, not allelic
Overall
CADD	34.0	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 0.000509% European (non-Finnish) · 6/1,179,680 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,613,570 alleles · very rare exomes 6/1,461,236 · genomes 0/152,334 · joint denominator

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.Glu200Val
Coding: c.599A>T
MANE Select: NM_003151
dbSNP: rs2470779371
Type: single nucleotide variant
Location: chr2:191066461 (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

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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-glu200val (accessed [today's date]).

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