Is PTEN p.Arg308fs (c.922del) pathogenic?

PTEN p.Arg308fs (c.922del) is classified Pathogenic in PTEN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-02). Absent from gnomAD; Associated with Cowden syndrome 1.

What condition is associated with PTEN p.Arg308fs (c.922del)?

PTEN p.Arg308fs (c.922del) is associated with Cowden syndrome 1 (ClinVar).

How common is PTEN p.Arg308fs (c.922del) in the general population?

PTEN p.Arg308fs (c.922del) is absent from gnomAD (gnomAD).

PTEN p.Arg308fs

c.922del · rs2493775879 · VCV2673933

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Cowden syndrome 1

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 8 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.13	GERP -4.9, phastCons 0.72

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.Arg308fs
Coding: c.922del
MANE Select: NM_000314
dbSNP: rs2493775879
Type: Deletion
Location: chr10:87961014 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 308: the c2 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

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

Similar variants

PTEN p.Arg308_Ala309insGluValTyrValIleLysLysSerIleAlaPheAlaValTer Pathogenic ★ same residue
PTEN p.Arg308Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
PTEN p.Arg308His Conflicting classifications of pathogenicity ★ ⚠ same residue
PTEN c.209+4_209+7del Pathogenic ★★★ same condition
PTEN c.210-2_211del Pathogenic ★★★ same condition
PTEN c.801+1del Pathogenic ★★★ same condition
PTEN p.Asn329fs Pathogenic ★★★ same condition
PTEN p.Gln17fs 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-arg308fs (accessed [today's date]).

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