Is STAT2 p.Ser80Cys (c.239C>G) pathogenic?

STAT2 p.Ser80Cys (c.239C>G) is classified Likely benign in STAT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely benign (0.0486); Very rare (popmax 0.00169%, nfe); Associated with Inborn genetic diseases.

What condition is associated with STAT2 p.Ser80Cys (c.239C>G)?

STAT2 p.Ser80Cys (c.239C>G) is associated with Inborn genetic diseases (ClinVar).

How common is STAT2 p.Ser80Cys (c.239C>G) in the general population?

STAT2 p.Ser80Cys (c.239C>G) is very rare (popmax 0.00169%, nfe) (gnomAD).

What do computational predictors say about STAT2 p.Ser80Cys (c.239C>G)?

AlphaMissense predicts likely benign (score 0.0486) — an in-silico prediction, not a clinical call.

STAT2 p.Ser80Cys

c.239C>G · VCV4632363

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0486 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00169%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0486	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -6.52	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 -3.1	GERP -3.4
Regional constraint	o/e 0.73	unconstrained · MANE · 13 kb · p 6.2e-18 · regional, not allelic
Overall
CADD	0.096	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 0.00169% European (non-Finnish) · 20/1,180,040 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.0013% 21/1,614,028 alleles · very rare exomes 18/1,461,836 · genomes 3/152,192 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00169%	59,002
African / African-American	0.00133%	74,916

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.Ser80Cys
Coding: c.239C>G
MANE Select: NM_005419
Type: single nucleotide variant
Location: chr12:56356178 (GRCh38)
Gene constraint: LOEUF 0.497 · pLI 0.81 (gnomAD)
Structure: AlphaFold pLDDT 78.45 · 6 PDB
Residue 80: 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

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-ser80cys (accessed [today's date]).

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