Is PTEN p.Glu7fs (c.21_22del) pathogenic?

PTEN p.Glu7fs (c.2122del) is classified Pathogenic in PTEN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-09-25). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with PTEN p.Glu7fs (c.21_22del)?

PTEN p.Glu7fs (c.21_22del) is associated with hereditary neoplastic syndrome, Cowden syndrome 1, PTEN hamartoma tumor syndrome (ClinVar).

How common is PTEN p.Glu7fs (c.21_22del) in the general population?

PTEN p.Glu7fs (c.21_22del) is absent from gnomAD (gnomAD).

PTEN p.Glu7fs

c.21_22del · rs786204881 · VCV189429

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 1 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 0.48, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PTEN
Protein: p.Glu7fs
Coding: c.21_22del
MANE Select: NM_000314
dbSNP: rs786204881
Type: Microsatellite
Location: chr10:87864487 (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

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

Also linked: Cowden syndrome 1 PTEN hamartoma tumor syndrome

Similar variants

PTEN p.Glu7Ter Pathogenic ★★ same residue
PTEN p.Glu7Asp Uncertain significance ★★ ⚠ same residue
PTEN p.Glu7= Likely benign ★ same residue
PTEN p.Asp52del Likely pathogenic ★★★ same condition
PTEN p.Ile33del Likely pathogenic ★★★ same condition
PTEN p.Tyr178del Likely pathogenic ★★★ same condition
PTEN p.Met199del Uncertain significance ★★★ same condition
PTEN c.165-24TTTG[2] Likely benign ★★★ 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-glu7fs (accessed [today's date]).

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