Is STAT1 p.Lys140fs (c.419_422del) pathogenic?

STAT1 p.Lys140fs (c.419422del) is classified Likely pathogenic in STAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-07). Very rare (popmax 0.00133%, afr).

How common is STAT1 p.Lys140fs (c.419_422del) in the general population?

STAT1 p.Lys140fs (c.419_422del) is very rare (popmax 0.00133%, afr) (gnomAD).

STAT1 p.Lys140fs

c.419_422del · rs755837357 · VCV523978

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 0.00133%, afr)

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 6 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.84	GERP -1.5, phastCons 0.003

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,034 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,614,082 alleles · very rare exomes 5/1,461,798 · genomes 0/152,284 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,034
European (non-Finnish)	0.000339%	294,990

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.Lys140fs
Coding: c.419_422del
MANE Select: NM_007315
dbSNP: rs755837357
Type: Deletion
Location: chr2:191001114 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 87.78 · 10 PDB
Residue 140: an α-helix

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

Similar variants

STAT1 p.Lys140= Likely benign ★ same residue
STAT1 p.Ile30fs Pathogenic ★★ same type
STAT1 p.Val339fs Pathogenic ★★ same type
STAT1 p.Asp257fs Pathogenic ★ same type
STAT1 p.Glu411fs Pathogenic ★ same type
STAT1 p.Ile232fs Pathogenic ★ same type
STAT1 p.Ile612fs Pathogenic ★ same type
STAT1 p.Leu667fs 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-lys140fs (accessed [today's date]).

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