Is STK11 p.Pro324= (c.972G>A) pathogenic?

STK11 p.Pro324= (c.972G>A) is classified Benign/Likely benign in STK11 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-01-27). Ultra-rare (popmax 0.0193%, sas); Associated with Peutz-Jeghers syndrome.

What condition is associated with STK11 p.Pro324= (c.972G>A)?

STK11 p.Pro324= (c.972G>A) is associated with Peutz-Jeghers syndrome, melanoma, cutaneous malignant, susceptibility to, 1, testicular germ cell tumor (ClinVar).

How common is STK11 p.Pro324= (c.972G>A) in the general population?

STK11 p.Pro324= (c.972G>A) is ultra-rare (popmax 0.0193%, sas) (gnomAD).

How is Peutz-Jeghers syndrome inherited?

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

STK11 p.Pro324=

c.972G>A · rs553474397 · VCV185194

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0193%, sas)

Conditions

Peutz-Jeghers syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.43 · evaluated, not missing
Constraint at this position
Conservation	phyloP -7.6	GERP -1.9
Overall
CADD	0.133	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0193% South Asian · 17/88,282 alleles

Filtering AF 0.0122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.00194% 31/1,595,434 alleles · ultra-rare exomes 28/1,443,182 · genomes 3/152,252 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0193%	5,193
African / African-American	0.00804%	12,440
Remaining individualsnot grpmax-eligible	0.00485%	20,603
East Asian	0.00227%	43,962
European (non-Finnish)	0.000341%	292,950

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.Pro324=
Coding: c.972G>A
MANE Select: NM_000455
dbSNP: rs553474397
Type: single nucleotide variant
Location: chr19:1223036 (GRCh38)
Gene constraint: LOEUF 0.364 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.27 · 4 PDB
Residue 324: an α-helix; the 'disordered' region; a UniProt-annotated variant site (in gastric carcinoma; no effect heterotrimeric complex assembly with strada and cab39)

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

Also linked: melanoma, cutaneous malignant, susceptibility to, 1 testicular germ cell tumor familial pancreatic carcinoma hereditary neoplastic syndrome

For Peutz-Jeghers syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

STK11 p.Pro324Arg Uncertain significance ★★ ⚠ same residue
STK11 p.Pro324Leu Uncertain significance ★★ ⚠ same residue
STK11 p.Pro324Ser Uncertain significance ★★ ⚠ same residue
STK11 p.Pro324Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
STK11 p.Pro324Gln Uncertain significance ★ ⚠ same residue
STK11 p.Pro324del Uncertain significance ★★ same residue
STK11 p.Pro324fs Pathogenic ★ 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-pro324 (accessed [today's date]).

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