Is STK11 p.Arg331= (c.993G>C) pathogenic?

STK11 p.Arg331= (c.993G>C) is classified Likely benign in STK11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-08). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with STK11 p.Arg331= (c.993G>C)?

STK11 p.Arg331= (c.993G>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is STK11 p.Arg331= (c.993G>C) in the general population?

STK11 p.Arg331= (c.993G>C) is absent from gnomAD v4.1 (gnomAD).

STK11 p.Arg331=

c.993G>C · rs1599929398 · VCV2586603

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -0.13	GERP -1.8, phastCons 0.19
Overall
CADD	4.218	PHRED · no single calibrated threshold — expert panels disagree

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.Arg331=
Coding: c.993G>C
MANE Select: NM_000455
dbSNP: rs1599929398
Type: single nucleotide variant
Location: chr19:1223057 (GRCh38)
Gene constraint: LOEUF 0.364 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.27 · 4 PDB
Residue 331: the 'disordered' region

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 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
STK11 c.464+1G>A Pathogenic/Likely pathogenic ★★ same condition
STK11 c.464+1G>T 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-arg331 (accessed [today's date]).

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