Is STAT1 p.Thr720Ile (c.2159C>T) pathogenic?

STAT1 p.Thr720Ile (c.2159C>T) is classified Likely pathogenic in STAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-01). AlphaMissense: likely benign (0.2559); Absent from gnomAD v4.1; Associated with Inherited Immunodeficiency Diseases.

What condition is associated with STAT1 p.Thr720Ile (c.2159C>T)?

STAT1 p.Thr720Ile (c.2159C>T) is associated with Inherited Immunodeficiency Diseases (ClinVar).

How common is STAT1 p.Thr720Ile (c.2159C>T) in the general population?

STAT1 p.Thr720Ile (c.2159C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STAT1 p.Thr720Ile (c.2159C>T)?

AlphaMissense predicts likely benign (score 0.2559) — an in-silico prediction, not a clinical call.

STAT1 p.Thr720Ile

c.2159C>T · rs1574636674 · VCV827739

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2559 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inherited Immunodeficiency Diseases

Computational evidence

Protein change
AlphaMissense	0.2559	likely benign ⚠ discordant with ClinVar
REVEL	0.456	indeterminate
SaProt	LLR -6.61	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.42	unconstrained · MANE · 15 kb · p 1.6e-32 · regional, not allelic
Overall
CADD	24.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: STAT1
Protein: p.Thr720Ile
Coding: c.2159C>T
MANE Select: NM_007315
dbSNP: rs1574636674
Type: single nucleotide variant
Location: chr2:190974909 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 87.78 · 10 PDB

Full STAT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inherited Immunodeficiency Diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

STAT1 p.Thr720= Likely benign ★ same residue
STAT1 p.Thr385Met Pathogenic ★★ same condition
STAT1 p.Arg70Pro Likely pathogenic ★ same condition
STAT1 p.Cys174Arg Likely pathogenic ★ ⚠ same condition
STAT1 p.Leu280Trp Likely pathogenic ★ same condition
STAT1 p.Tyr287Asp Likely pathogenic ★ ⚠ same condition
STAT1 p.Glu284Lys Conflicting classifications of pathogenicity ★ ⚠ same condition
STAT1 p.Ala267Val Pathogenic ★★ ⚠ same type

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/stat1-p-thr720ile (accessed [today's date]).

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