Is STK11 p.Phe12= (c.36C>T) pathogenic?

STK11 p.Phe12= (c.36C>T) is classified Benign/Likely benign in STK11 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-12). Very rare (popmax 8.5e-05%, nfe); Associated with Peutz-Jeghers syndrome.

What condition is associated with STK11 p.Phe12= (c.36C>T)?

STK11 p.Phe12= (c.36C>T) is associated with Peutz-Jeghers syndrome (ClinVar).

How common is STK11 p.Phe12= (c.36C>T) in the general population?

STK11 p.Phe12= (c.36C>T) is very rare (popmax 8.5e-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.Phe12=

c.36C>T · rs2145404533 · VCV2723627

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.5e-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 0.15	GERP -1.7, phastCons 0.34
Overall
CADD	9.708	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.5e-05% European (non-Finnish) · 1/1,175,860 alleles

Overall 6.23e-05% 1/1,604,442 alleles · very rare exomes 1/1,452,228 · genomes 0/152,214 · 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.Phe12=
Coding: c.36C>T
MANE Select: NM_000455
dbSNP: rs2145404533
Type: single nucleotide variant
Location: chr19:1206949 (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 c.290+1G>A Pathogenic ★★ same condition
STK11 c.290+1G>C Pathogenic ★★ same condition
STK11 c.290+1G>T Pathogenic ★★ same condition
STK11 c.290+2T>A Pathogenic/Likely pathogenic ★★ same condition
STK11 c.291-2A>G Pathogenic ★★ same condition
STK11 c.374+1A>G Pathogenic ★★ same condition
STK11 c.464+1G>A Pathogenic/Likely pathogenic ★★ same condition
STK11 c.464+1G>T 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-phe12 (accessed [today's date]).

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