Is STK11 p.Pro149= (c.447A>G) pathogenic?

STK11 p.Pro149= (c.447A>G) is classified Conflicting classifications of pathogenicity in STK11 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-03-26). Very rare (popmax 0.00175%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with STK11 p.Pro149= (c.447A>G)?

STK11 p.Pro149= (c.447A>G) is associated with hereditary neoplastic syndrome, Peutz-Jeghers syndrome (ClinVar).

How common is STK11 p.Pro149= (c.447A>G) in the general population?

STK11 p.Pro149= (c.447A>G) is very rare (popmax 0.00175%, nfe) (gnomAD).

STK11 p.Pro149=

c.447A>G · rs587780718 · VCV135922

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00175%, nfe)

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 -15	GERP -2.5
Overall
CADD	0.242	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00175% European (non-Finnish) · 19/1,086,990 alleles

Filtering AF 0.00112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000901%

Overall 0.00138% 20/1,451,904 alleles · very rare exomes 18/1,304,774 · genomes 2/147,130 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00175%	57,210
South Asian	0.00117%	85,818

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.Pro149=
Coding: c.447A>G
MANE Select: NM_000455
dbSNP: rs587780718
Type: single nucleotide variant
Location: chr19:1219396 (GRCh38)
Gene constraint: LOEUF 0.364 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.27 · 4 PDB
Residue 149: 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.Pro149Leu Uncertain significance ★ ⚠ same residue
STK11 p.Pro149Ser Uncertain significance ★ ⚠ same residue
STK11 p.Pro149fs Pathogenic ★★ same residue
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.291-1G>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-pro149 (accessed [today's date]).

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