Is STK11 p.Ile111fs (c.332_333insG) pathogenic?

STK11 p.Ile111fs (c.332333insG) is classified Pathogenic in STK11 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-11). No gnomAD frequency available for this variant; Associated with Peutz-Jeghers syndrome.

What condition is associated with STK11 p.Ile111fs (c.332_333insG)?

STK11 p.Ile111fs (c.332_333insG) is associated with Peutz-Jeghers syndrome (ClinVar).

How common is STK11 p.Ile111fs (c.332_333insG) in the general population?

STK11 p.Ile111fs (c.332_333insG) is no gnomAD frequency available for this variant (gnomAD).

How is Peutz-Jeghers syndrome inherited?

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

STK11 p.Ile111fs

c.332_333insG · rs2145420699 · VCV1073934

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Peutz-Jeghers syndrome

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 haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 2 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 0.92, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: STK11
Protein: p.Ile111fs
Coding: c.332_333insG
MANE Select: NM_000455
dbSNP: rs2145420699
Type: Insertion
Location: chr19:1218458 (GRCh38)
Gene constraint: LOEUF 0.364 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.27 · 4 PDB
Residue 111: the protein kinase domain

Full STK11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Peutz-Jeghers syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Peutz-Jeghers syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

STK11 p.Glu265delinsPhePhePhePhePhePheXaaXaaXaaXaaAlaLeuLeuThrSerTer Pathogenic ★ same condition
STK11 p.Lys83delinsAlaGlyArgGlyGlySerArgLeuTer Pathogenic ★ same condition
STK11 c.597+10_597+11insCTAG Conflicting classifications of pathogenicity ★ same condition
STK11 p.Ile111Asn Uncertain significance ★ ⚠ same residue
STK11 p.Ser419fs Uncertain significance ★ same condition
STK11 c.1109-6_1109-5insGTGCCGTCTCCCT Likely benign ★ same condition
STK11 c.597+16_597+17insTA Likely benign ★ same condition
STK11 p.Ile111= Likely benign ★ same residue

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/stk11-p-ile111fs (accessed [today's date]).

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