Is PTEN p.Lys6Glu (c.16A>G) pathogenic?

PTEN p.Lys6Glu (c.16A>G) is classified Pathogenic in PTEN (ClinVar, Expert panel, 5 submitters; last evaluated 2021-06-04). AlphaMissense: likely pathogenic (0.9903); Absent from gnomAD v4.1; Associated with PTEN hamartoma tumor syndrome.

What condition is associated with PTEN p.Lys6Glu (c.16A>G)?

PTEN p.Lys6Glu (c.16A>G) is associated with PTEN hamartoma tumor syndrome, familial meningioma, hereditary neoplastic syndrome (ClinVar).

How common is PTEN p.Lys6Glu (c.16A>G) in the general population?

PTEN p.Lys6Glu (c.16A>G) is absent from gnomAD v4.1 (gnomAD).

How is PTEN hamartoma tumor syndrome inherited?

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

What do computational predictors say about PTEN p.Lys6Glu (c.16A>G)?

AlphaMissense predicts likely pathogenic (score 0.9903) — an in-silico prediction, not a clinical call.

PTEN p.Lys6Glu

c.16A>G · rs1589596143 · VCV644390

Pathogenic Expert panel

Classification

Pathogenic

ClinVar

Review

Expert panel ★★★☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.9903 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

PTEN hamartoma tumor syndrome

ClinGen expert panel — PTEN VCEP

Pathogenic for PTEN hamartoma tumor syndrome. Applied ACMG criteria (verbatim):

PM2 PS2_VeryStrong PS3_Supporting PS4_Moderate PP2

Curation rationale (ClinGen, verbatim)

PTEN c.16A>G (p.Lys6Glu) meets criteria to be classified as pathogenic for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (PMID 30311380). Please see a summary of the rules and criteria codes in the “PTEN ACMG Specifications Summary” document (assertion method column). PS2_VS: One proven plus two assumed de novo observations in a patient with the disease and no family history. (internal laboratory contributor(s) SCV001369131.2, SCV001819316.1) PS4_M: Probands with phenotype specificity score of 2-3.5. (internal laboratory contributor(s) SCV001819316.1) PM2: Absent in large sequenced populations (PMID 27535533). PP2: PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease. PS3_P: Abnormal in vitro cellular assay or transgenic model with phenotype different from wild type that does not meet PS3. (PMID 32366478, PMID 32350270, PMID 29706350)

ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.

Computational evidence

Protein change
AlphaMissense	0.9903	likely pathogenic ✓ concordant with ClinVar
REVEL	0.89	moderately pathogenic-leaning
SaProt	LLR -12.86	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 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 69 kb · p 6.5e-17 · regional, not allelic
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

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: PTEN
Protein: p.Lys6Glu
Coding: c.16A>G
MANE Select: NM_000314
dbSNP: rs1589596143
Type: single nucleotide variant
Location: chr10:87864485 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB

Full PTEN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PTEN hamartoma tumor syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial meningioma hereditary neoplastic syndrome

For PTEN hamartoma tumor syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

PTEN p.Lys6= Likely benign ★★★ same residue
PTEN p.Lys6Arg Uncertain significance ★★ ⚠ same residue
PTEN p.Lys6Thr Uncertain significance ★★ ⚠ same residue
PTEN p.Lys6Asn Uncertain significance ★ ⚠ same residue
PTEN p.Lys6fs Pathogenic ★★ same residue
PTEN p.Lys6Ile Likely pathogenic ★ same residue
PTEN c.1026+1G>A Pathogenic ★★★ same condition
PTEN c.1027-1852A>G Likely 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/pten-p-lys6glu (accessed [today's date]).

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