Is STK11 p.Arg40= (c.120C>G) pathogenic?

STK11 p.Arg40= (c.120C>G) is classified Likely benign in STK11 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-22). Very rare (popmax 8.48e-05%, nfe); Associated with Peutz-Jeghers syndrome.

What condition is associated with STK11 p.Arg40= (c.120C>G)?

STK11 p.Arg40= (c.120C>G) is associated with Peutz-Jeghers syndrome (ClinVar).

How common is STK11 p.Arg40= (c.120C>G) in the general population?

STK11 p.Arg40= (c.120C>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Peutz-Jeghers syndrome inherited?

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

STK11 p.Arg40=

c.120C>G · rs878853984 · VCV1096521

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

Peutz-Jeghers syndrome

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 0.17	GERP -1.8, phastCons 0.96
Overall
CADD	13.21	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,864 alleles

Overall 6.2e-05% 1/1,613,796 alleles · very rare exomes 1/1,461,626 · genomes 0/152,170 · 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: STK11
Protein: p.Arg40=
Coding: c.120C>G
MANE Select: NM_000455
dbSNP: rs878853984
Type: single nucleotide variant
Location: chr19:1207033 (GRCh38)
Gene constraint: LOEUF 0.364 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.27 · 4 PDB

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.Arg40Gly Uncertain significance ★ ⚠ same residue
STK11 p.Arg40fs Pathogenic ★★ same residue
STK11 p.Arg40del Uncertain significance ★★ same residue
STK11 p.Arg40Cys Uncertain significance ★ ⚠ same residue
STK11 p.Arg40His Uncertain significance ★ same residue
STK11 p.Arg40Leu Uncertain significance ★ ⚠ same residue
STK11 c.290+1G>A Pathogenic ★★ same condition
STK11 c.290+1G>C 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/stk11-p-arg40 (accessed [today's date]).

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