Is PTEN p.Gln97Ter (c.289C>T) pathogenic?

PTEN p.Gln97Ter (c.289C>T) is classified Pathogenic in PTEN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-03-09). Very rare (popmax 0.00134%, afr); Associated with Cowden syndrome 1.

What condition is associated with PTEN p.Gln97Ter (c.289C>T)?

PTEN p.Gln97Ter (c.289C>T) is associated with Cowden syndrome 1, macrocephaly-autism syndrome, familial meningioma (ClinVar).

How common is PTEN p.Gln97Ter (c.289C>T) in the general population?

PTEN p.Gln97Ter (c.289C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

PTEN p.Gln97Ter

c.289C>T · rs786204928 · VCV189483

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

Cowden syndrome 1

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 5 of 9
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Overall
CADD	41.0	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 0.00134% African / African-American · 1/74,890 alleles

Overall 0.000124% 2/1,613,058 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,890
European (non-Finnish)	8.48e-05%	1,179,204

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.Gln97Ter
Coding: c.289C>T
MANE Select: NM_000314
dbSNP: rs786204928
Type: single nucleotide variant
Location: chr10:87933048 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 97: an α-helix; 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

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

Also linked: macrocephaly-autism syndrome familial meningioma glioma susceptibility 2 hereditary neoplastic syndrome PTEN hamartoma tumor syndrome prostate cancer, hereditary

Similar variants

PTEN p.Gln97Glu Uncertain significance ★★ ⚠ same residue
PTEN p.Gln97= Benign/Likely benign ★★ same residue
PTEN p.Gln97Arg Uncertain significance ★ ⚠ same residue
PTEN p.Gln97His Uncertain significance ★ ⚠ same residue
PTEN p.Gln97fs Pathogenic ★ same residue
PTEN p.Gln97Leu 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-gln97ter (accessed [today's date]).

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