Is STAT2 p.Ala302Thr (c.904G>A) pathogenic?

STAT2 p.Ala302Thr (c.904G>A) is classified Uncertain significance in STAT2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-20). AlphaMissense: likely benign (0.0863); Ultra-rare (popmax 0.0267%, afr); Associated with Inborn genetic diseases.

What condition is associated with STAT2 p.Ala302Thr (c.904G>A)?

STAT2 p.Ala302Thr (c.904G>A) is associated with Inborn genetic diseases, primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection (ClinVar).

How common is STAT2 p.Ala302Thr (c.904G>A) in the general population?

STAT2 p.Ala302Thr (c.904G>A) is ultra-rare (popmax 0.0267%, afr) (gnomAD).

What do computational predictors say about STAT2 p.Ala302Thr (c.904G>A)?

AlphaMissense predicts likely benign (score 0.0863) — an in-silico prediction, not a clinical call.

STAT2 p.Ala302Thr

c.904G>A · rs141205552 · VCV859938

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0863 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0863	likely benign
REVEL	0.156	moderately benign-leaning
SaProt	LLR -5.92	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 3.5	GERP 1.4, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 13 kb · p 6.2e-18 · regional, not allelic
Overall
CADD	23.6	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 0.0267% African / African-American · 20/75,034 alleles

Filtering AF 0.0177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.00235% 38/1,614,124 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0267%	3,752
East Asian	0.0178%	5,610
Admixed American	0.00167%	60,012
Remaining individualsnot grpmax-eligible	0.0016%	62,504
European (non-Finnish)	0.000678%	147,500

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: STAT2
Protein: p.Ala302Thr
Coding: c.904G>A
MANE Select: NM_005419
dbSNP: rs141205552
Type: single nucleotide variant
Location: chr12:56351329 (GRCh38)
Gene constraint: LOEUF 0.497 · pLI 0.81 (gnomAD)
Structure: AlphaFold pLDDT 78.45 · 6 PDB
Residue 302: the 'mediates interaction with usp18' region; an α-helix

Full STAT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection

Similar variants

STAT2 p.Arg667Ter Pathogenic/Likely pathogenic ★★ same condition
STAT2 p.Gln274Ter Pathogenic/Likely pathogenic ★★ same condition
STAT2 p.Ala219Thr Uncertain significance ★★ ⚠ same condition
STAT2 p.Arg300Cys Uncertain significance ★★ ⚠ same condition
STAT2 p.Arg330Gln Uncertain significance ★★ ⚠ same condition
STAT2 p.Arg409His Uncertain significance ★★ ⚠ same condition
STAT2 p.Arg510Gln Uncertain significance ★★ ⚠ same condition
STAT2 p.Arg544Gln Uncertain significance ★★ ⚠ same condition

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/stat2-p-ala302thr (accessed [today's date]).

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