Is STAT1 p.Leu79Val (c.235C>G) pathogenic?

STAT1 p.Leu79Val (c.235C>G) is classified Uncertain significance in STAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: ambiguous (0.3842); Absent from gnomAD v4.1; Associated with autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome.

How common is STAT1 p.Leu79Val (c.235C>G) in the general population?

STAT1 p.Leu79Val (c.235C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STAT1 p.Leu79Val (c.235C>G)?

AlphaMissense predicts ambiguous (score 0.3842) — an in-silico prediction, not a clinical call.

STAT1 p.Leu79Val

Q: What condition is associated with STAT1 p.Leu79Val (c.235C>G)?

STAT1 p.Leu79Val (c.235C>G) is associated with autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome (ClinVar).

Q: How is STAT1-related autoimmune enteropathy and endocrinopathy-susceptibility to chronic infections syndrome inherited?

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

c.235C>G · VCV4533380

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3842 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome

Computational evidence

Protein change
AlphaMissense	0.3842	ambiguous
REVEL	0.341	indeterminate
SaProt	LLR -4.38	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -1.9, phastCons 1
Regional constraint	o/e 0.31	constrained · MANE · 2,434 bp · p 7.1e-17 · regional, not allelic
Overall
CADD	19.94	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.Leu79Val
Coding: c.235C>G
MANE Select: NM_007315
Type: single nucleotide variant
Location: chr2:191009001 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 87.78 · 10 PDB
Residue 79: an α-helix

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

Disease context

autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For STAT1-related autoimmune enteropathy and endocrinopathy-susceptibility to chronic infections syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy

Similar variants

STAT1 p.Leu79= Likely benign ★ same residue
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

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-leu79val (accessed [today's date]).

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