Is STAT1 p.Pro533= (c.1599C>T) pathogenic?

STAT1 p.Pro533= (c.1599C>T) is classified Likely benign in STAT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-10). Very rare (popmax 0.00445%, eas); Associated with immunodeficiency 31B.

How common is STAT1 p.Pro533= (c.1599C>T) in the general population?

STAT1 p.Pro533= (c.1599C>T) is very rare (popmax 0.00445%, eas) (gnomAD).

STAT1 p.Pro533=

Q: What condition is associated with STAT1 p.Pro533= (c.1599C>T)?

STAT1 p.Pro533= (c.1599C>T) is associated with immunodeficiency 31B, autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome, Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency (ClinVar).

Q: How is Susceptibility to viral and mycobacterial infections due to STAT1 deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1599C>T · rs747857564 · VCV1595193

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00445%, eas)

Conditions

immunodeficiency 31B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -3.4
Overall
CADD	0.112	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00445% East Asian · 2/44,898 alleles

Filtering AF 0.000738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000867% 14/1,614,072 alleles · very rare exomes 11/1,461,882 · genomes 3/152,190 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00445%	22,449
Remaining individualsnot grpmax-eligible	0.0016%	62,490
African / African-American	0.00133%	74,910
European (non-Finnish)	0.000847%	118,004

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: STAT1
Protein: p.Pro533=
Coding: c.1599C>T
MANE Select: NM_007315
dbSNP: rs747857564
Type: single nucleotide variant
Location: chr2:190980653 (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

immunodeficiency 31B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency

For Susceptibility to viral and mycobacterial infections due to STAT1 deficiency (Orphanet):

Inheritance: Autosomal recessive

Similar variants

STAT1 p.Ala267Val Pathogenic ★★ ⚠ same condition
STAT1 p.Arg274Gln Pathogenic ★★ ⚠ same condition
STAT1 p.Arg274Gly Pathogenic/Likely pathogenic ★★ same condition
STAT1 p.Arg274Trp Pathogenic ★★ same condition
STAT1 p.Asp171Asn Likely pathogenic ★★ ⚠ same condition
STAT1 p.Asp292Glu Likely pathogenic ★★ ⚠ same condition
STAT1 p.Cys324Arg Likely pathogenic ★★ same condition
STAT1 p.Gln271Pro Pathogenic/Likely pathogenic ★★ ⚠ 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/stat1-p-pro533 (accessed [today's date]).

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