Is STAT2 p.Gln629Pro (c.1886A>C) pathogenic?

STAT2 p.Gln629Pro (c.1886A>C) is classified Uncertain significance in STAT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-02). AlphaMissense: likely benign (0.1606); Very rare (popmax 0.0039%, nfe); Associated with Inborn genetic diseases.

What condition is associated with STAT2 p.Gln629Pro (c.1886A>C)?

STAT2 p.Gln629Pro (c.1886A>C) is associated with Inborn genetic diseases (ClinVar).

How common is STAT2 p.Gln629Pro (c.1886A>C) in the general population?

STAT2 p.Gln629Pro (c.1886A>C) is very rare (popmax 0.0039%, nfe) (gnomAD).

What do computational predictors say about STAT2 p.Gln629Pro (c.1886A>C)?

AlphaMissense predicts likely benign (score 0.1606) — an in-silico prediction, not a clinical call.

STAT2 p.Gln629Pro

c.1886A>C · VCV4840839

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1606 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0039%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1606	likely benign
REVEL	0.786	moderately pathogenic-leaning
SaProt	LLR -8.89	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.2	GERP 1.9, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 13 kb · p 6.2e-18 · regional, not allelic
Overall
CADD	25.0	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 0.0039% European (non-Finnish) · 46/1,179,826 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00267%

Overall 0.0031% 50/1,613,954 alleles · very rare exomes 50/1,461,656 · genomes 0/152,298 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0039%	25,648
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
Remaining individualsnot grpmax-eligible	0.0032%	31,250
South Asian	0.0011%	91,080

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.Gln629Pro
Coding: c.1886A>C
MANE Select: NM_005419
Type: single nucleotide variant
Location: chr12:56346600 (GRCh38)
Gene constraint: LOEUF 0.497 · pLI 0.81 (gnomAD)
Structure: AlphaFold pLDDT 78.45 · 6 PDB
Residue 629: the sh2 domain

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

Similar variants

STAT2 p.Ala219Thr Uncertain significance ★★ ⚠ same condition
STAT2 p.Ala302Thr Uncertain significance ★★ ⚠ same condition
STAT2 p.Arg300Cys Uncertain significance ★★ ⚠ same condition
STAT2 p.Arg409His Uncertain significance ★★ ⚠ same condition
STAT2 p.Arg576Cys Uncertain significance ★★ ⚠ same condition
STAT2 p.Arg646Cys Uncertain significance ★★ ⚠ same condition
STAT2 p.Asn700Ser Uncertain significance ★★ ⚠ same condition
STAT2 p.Asp558Glu 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-gln629pro (accessed [today's date]).

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