Is STAT1 p.Pro251fs (c.750dup) pathogenic?

STAT1 p.Pro251fs (c.750dup) is classified Likely pathogenic in STAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-09-11). Very rare (popmax 0.0011%, sas).

How common is STAT1 p.Pro251fs (c.750dup) in the general population?

STAT1 p.Pro251fs (c.750dup) is very rare (popmax 0.0011%, sas) (gnomAD).

STAT1 p.Pro251fs

c.750dup · rs1341038926 · VCV524113

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 9 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,082 alleles

Overall 6.2e-05% 1/1,614,114 alleles · very rare exomes 1/1,461,884 · genomes 0/152,230 · joint denominator

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.Pro251fs
Coding: c.750dup
MANE Select: NM_007315
dbSNP: rs1341038926
Type: Duplication
Location: chr2:190997890 (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

Similar variants

STAT1 p.Pro251= Likely benign ★★ same residue
STAT1 p.Pro251Leu Likely pathogenic ★ same residue
STAT1 c.1098-5dup Benign/Likely benign ★★ same type
STAT1 c.1633-13dup Likely benign ★★ same type
STAT1 p.Ser25fs Pathogenic ★ same type
STAT1 p.Thr227fs Pathogenic ★ same type
STAT1 p.Leu667_Tyr668insLysTyrLeu Uncertain significance ★ same type
STAT1 c.1038-9dup Benign ★ 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-pro251fs (accessed [today's date]).

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