Is PTEN p.Arg233Ter (c.697C>T) pathogenic?

PTEN p.Arg233Ter (c.697C>T) is classified Pathogenic/Likely pathogenic in PTEN (ClinVar, Multiple submitters, 37 submitters; last evaluated 2026-05-14). Very rare (popmax 0.00167%, amr); Associated with PTEN-related disorder.

What condition is associated with PTEN p.Arg233Ter (c.697C>T)?

PTEN p.Arg233Ter (c.697C>T) is associated with PTEN-related disorder, gastric cancer, Cowden syndrome 1 (ClinVar).

How common is PTEN p.Arg233Ter (c.697C>T) in the general population?

PTEN p.Arg233Ter (c.697C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

PTEN p.Arg233Ter

c.697C>T · rs121909219 · VCV7813

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 37 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

PTEN-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 7 of 9
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP 0.041, phastCons 0.91
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,010 alleles

Overall 6.84e-05% 1/1,461,758 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.

Cancer therapy — CIViC

Disease	Therapies	Level	Significance
Breast Cancer	MTOR Inhibitor	D	Sensitivity/Response
Glioblastoma		B	Poor Outcome

Variant & gene context

Gene: PTEN
Protein: p.Arg233Ter
Coding: c.697C>T
MANE Select: NM_000314
dbSNP: rs121909219
Type: single nucleotide variant
Location: chr10:87957915 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 233: a β-strand; 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

PTEN-related disorder

Also linked: gastric cancer Cowden syndrome 1 macrocephaly-autism syndrome glioma susceptibility 2 hereditary neoplastic syndrome Cowden disease PTEN hamartoma tumor syndrome ovarian neoplasm

Similar variants

PTEN p.Arg233Gln Uncertain significance ★★★ ⚠ same residue
PTEN p.Arg233Gly Uncertain significance ★★ ⚠ same residue
PTEN p.Arg233= Benign/Likely benign ★★ same residue
PTEN p.Arg233fs 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

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-arg233ter (accessed [today's date]).

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