Is PTEN p.Glu40= (c.120A>G) pathogenic?

PTEN p.Glu40= (c.120A>G) is classified Benign/Likely benign in PTEN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-11). Absent from gnomAD v4.1; Associated with Cowden syndrome 1.

What condition is associated with PTEN p.Glu40= (c.120A>G)?

PTEN p.Glu40= (c.120A>G) is associated with Cowden syndrome 1, hereditary neoplastic syndrome (ClinVar).

How common is PTEN p.Glu40= (c.120A>G) in the general population?

PTEN p.Glu40= (c.120A>G) is absent from gnomAD v4.1 (gnomAD).

PTEN p.Glu40=

c.120A>G · rs1250521901 · VCV2607952

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cowden syndrome 1

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 · A>T here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 1.2, phastCons 1
Overall
CADD	13.2	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: PTEN
Protein: p.Glu40=
Coding: c.120A>G
MANE Select: NM_000314
dbSNP: rs1250521901
Type: single nucleotide variant
Location: chr10:87894065 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 40: a β-strand; the phosphatase tensin-type domain

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

Disease context

Cowden syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

Similar variants

PTEN p.Glu40Ter Pathogenic ★★ same residue
PTEN p.Glu40fs Pathogenic ★ same residue
PTEN c.1026+1G>A Pathogenic ★★★ same condition
PTEN c.1027-1852A>G Likely pathogenic ★★★ same condition
PTEN c.1027-1G>A Pathogenic ★★★ same condition
PTEN c.165-1G>A Likely pathogenic ★★★ same condition
PTEN c.165-1G>C Pathogenic ★★★ same condition
PTEN c.209+4A>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/pten-p-glu40 (accessed [today's date]).

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