Is PTEN p.Lys164= (c.492G>A) pathogenic?

PTEN p.Lys164= (c.492G>A) is classified Conflicting classifications of pathogenicity in PTEN (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2024-11-19). Very rare (popmax 0.00536%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with PTEN p.Lys164= (c.492G>A)?

PTEN p.Lys164= (c.492G>A) is associated with hereditary neoplastic syndrome, PTEN hamartoma tumor syndrome (ClinVar).

How common is PTEN p.Lys164= (c.492G>A) in the general population?

PTEN p.Lys164= (c.492G>A) is very rare (popmax 0.00536%, afr) (gnomAD).

PTEN p.Lys164=

c.492G>A · rs146629065 · VCV421963

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00536%, afr)

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 12	GERP 2.4, phastCons 1
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00536% African / African-American · 4/74,692 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00263% 4/151,992 alleles · very rare

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: PTEN
Protein: p.Lys164=
Coding: c.492G>A
MANE Select: NM_000314
dbSNP: rs146629065
Type: single nucleotide variant
Location: chr10:87933251 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 164: the phosphatase tensin-type domain; a UniProt-annotated variant site (in mcephas)

Full PTEN 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: PTEN hamartoma tumor syndrome

Similar variants

PTEN p.Lys164Ter Pathogenic ★★ same residue
PTEN p.Lys164Glu Uncertain significance ★★ ⚠ same residue
PTEN p.Lys164Met Uncertain significance ★ ⚠ same residue
PTEN p.Lys164fs Pathogenic ★★ same residue
PTEN p.Lys164Asn Uncertain significance ★ ⚠ same residue
PTEN p.Lys164Arg Uncertain significance ⚠ 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-lys164 (accessed [today's date]).

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