Is STK11 p.Ser142= (c.426C>T) pathogenic?

STK11 p.Ser142= (c.426C>T) is classified Benign/Likely benign in STK11 (ClinVar, Multiple submitters, 17 submitters; last evaluated 2026-05-01). Rare (popmax 0.224%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with STK11 p.Ser142= (c.426C>T)?

STK11 p.Ser142= (c.426C>T) is associated with hereditary neoplastic syndrome, Peutz-Jeghers syndrome (ClinVar).

How common is STK11 p.Ser142= (c.426C>T) in the general population?

STK11 p.Ser142= (c.426C>T) is rare (popmax 0.224%, amr) (gnomAD).

STK11 p.Ser142=

c.426C>T · rs758448869 · VCV183890

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 17 submitters

gnomAD v4.1

Rare

rare (popmax 0.224%, amr)

Conditions

hereditary neoplastic 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 · C>G here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP -8.2	GERP -2.5
Overall
CADD	1.424	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.224% Admixed American · 127/56,746 alleles

Filtering AF 0.192% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.18%

Overall 0.0112% 174/1,555,346 alleles · rare exomes 95/1,405,192 · genomes 79/150,154 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.224%	447
Middle Eastern	0.0518%	1,929
Remaining individualsnot grpmax-eligible	0.0153%	6,556
Finnishnot grpmax-eligible	0.00346%	28,867
European (non-Finnish)	0.00287%	34,868

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.Ser142=
Coding: c.426C>T
MANE Select: NM_000455
dbSNP: rs758448869
Type: single nucleotide variant
Location: chr19:1219375 (GRCh38)
Gene constraint: LOEUF 0.364 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.27 · 4 PDB
Residue 142: an α-helix; 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.Ser142Asn Uncertain significance ★★ ⚠ same residue
STK11 p.Ser142Gly Uncertain significance ★★ ⚠ 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-ser142 (accessed [today's date]).

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