Is STK11 p.Phe234Cys (c.701T>G) pathogenic?

STK11 p.Phe234Cys (c.701T>G) is classified Uncertain significance in STK11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-15). AlphaMissense: likely pathogenic (0.6056); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with STK11 p.Phe234Cys (c.701T>G)?

STK11 p.Phe234Cys (c.701T>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is STK11 p.Phe234Cys (c.701T>G) in the general population?

STK11 p.Phe234Cys (c.701T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STK11 p.Phe234Cys (c.701T>G)?

AlphaMissense predicts likely pathogenic (score 0.6056) — an in-silico prediction, not a clinical call.

STK11 p.Phe234Cys

c.701T>G · VCV3802381

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6056 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.6056	likely pathogenic
REVEL	0.685	pathogenic-leaning
SaProt	LLR -13.71	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 2,648 bp · p 1.4e-12 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: STK11
Protein: p.Phe234Cys
Coding: c.701T>G
MANE Select: NM_000455
Type: single nucleotide variant
Location: chr19:1220684 (GRCh38)
Gene constraint: LOEUF 0.364 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.27 · 4 PDB
Residue 234: 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

Similar variants

STK11 p.Phe234= Benign/Likely benign ★★ same residue
STK11 p.Phe234Leu Uncertain significance ★ ⚠ same residue
STK11 c.290+1G>A 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
STK11 c.374+1A>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-phe234cys (accessed [today's date]).

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