Is STAT4 p.Arg87Lys (c.260G>A) pathogenic?

STAT4 p.Arg87Lys (c.260G>A) is classified Uncertain significance in STAT4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-21). AlphaMissense: likely benign (0.0914); Ultra-rare (popmax 0.0234%, amr).

How common is STAT4 p.Arg87Lys (c.260G>A) in the general population?

STAT4 p.Arg87Lys (c.260G>A) is ultra-rare (popmax 0.0234%, amr) (gnomAD).

What do computational predictors say about STAT4 p.Arg87Lys (c.260G>A)?

AlphaMissense predicts likely benign (score 0.0914) — an in-silico prediction, not a clinical call.

STAT4 p.Arg87Lys

c.260G>A · rs202184860 · VCV1447122

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0914 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0234%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0914	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -5.40	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 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 114 kb · p 8.5e-09 · regional, not allelic
Overall
CADD	17.94	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 0.0234% Admixed American · 12/51,232 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0105%

Overall 0.000966% 15/1,552,470 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0234%	4,269
African / African-American	0.00138%	72,440
European (non-Finnish)	0.000174%	575,609

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.Arg87Lys
Coding: c.260G>A
MANE Select: NM_003151
dbSNP: rs202184860
Type: single nucleotide variant
Location: chr2:191146626 (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.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-arg87lys (accessed [today's date]).

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