Is STK11 p.Arg147= (c.441T>C) pathogenic?

STK11 p.Arg147= (c.441T>C) is classified Benign/Likely benign in STK11 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-10-29). Very rare (popmax 0.00138%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with STK11 p.Arg147= (c.441T>C)?

STK11 p.Arg147= (c.441T>C) is associated with hereditary neoplastic syndrome, Peutz-Jeghers syndrome (ClinVar).

How common is STK11 p.Arg147= (c.441T>C) in the general population?

STK11 p.Arg147= (c.441T>C) is very rare (popmax 0.00138%, afr) (gnomAD).

STK11 p.Arg147=

c.441T>C · rs786201456 · VCV184427

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00138%, afr)

Conditions

hereditary neoplastic 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 -1.7	GERP -2.5
Overall
CADD	3.183	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00138% African / African-American · 1/72,556 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000195% 3/1,538,990 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00138%	72,556
European (non-Finnish)	0.000175%	571,099

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.Arg147=
Coding: c.441T>C
MANE Select: NM_000455
dbSNP: rs786201456
Type: single nucleotide variant
Location: chr19:1219390 (GRCh38)
Gene constraint: LOEUF 0.364 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.27 · 4 PDB
Residue 147: the protein kinase domain

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Peutz-Jeghers syndrome

Similar variants

STK11 p.Arg147Pro Likely pathogenic ★ same residue
STK11 p.Arg147Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
STK11 p.Arg147Gly Uncertain significance ★ same residue
STK11 p.Arg147His Conflicting classifications of pathogenicity ★ ⚠ same residue
STK11 p.Arg147Ser Uncertain significance ★ ⚠ same residue
STK11 p.Arg147fs Pathogenic same residue
STK11 p.Arg147Leu Uncertain significance ★ same residue
STK11 c.290+1G>A 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-arg147 (accessed [today's date]).

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