Is STK11 p.Pro144= (c.432G>A) pathogenic?

STK11 p.Pro144= (c.432G>A) is classified Benign/Likely benign in STK11 (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-01-19). Ultra-rare (popmax 0.0165%, mid); Associated with hereditary neoplastic syndrome.

What condition is associated with STK11 p.Pro144= (c.432G>A)?

STK11 p.Pro144= (c.432G>A) is associated with hereditary neoplastic syndrome, Peutz-Jeghers syndrome (ClinVar).

How common is STK11 p.Pro144= (c.432G>A) in the general population?

STK11 p.Pro144= (c.432G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

STK11 p.Pro144=

c.432G>A · rs376788924 · VCV183815

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 -20	GERP -2.5
Overall
CADD	1.066	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,048 alleles

Filtering AF 0.00784% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00611%

Overall 0.00307% 49/1,598,386 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,048
South Asian	0.0136%	7,346
Finnishnot grpmax-eligible	0.00973%	10,281
African / African-American	0.00936%	10,687
Ashkenazi Jewishnot grpmax-eligible	0.00683%	14,631
East Asian	0.00227%	44,146
Admixed American	0.00172%	58,150
Remaining individualsnot grpmax-eligible	0.00161%	61,936
European (non-Finnish)	0.00153%	65,182

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.Pro144=
Coding: c.432G>A
MANE Select: NM_000455
dbSNP: rs376788924
Type: single nucleotide variant
Location: chr19:1219381 (GRCh38)
Gene constraint: LOEUF 0.364 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.27 · 4 PDB
Residue 144: 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.Pro144Leu Uncertain significance ★★ ⚠ same residue
STK11 p.Pro144fs 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
STK11 c.291-2A>G 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-pro144 (accessed [today's date]).

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