Is PTEN c.209+2T>C pathogenic?

PTEN c.209+2T>C is classified Pathogenic/Likely pathogenic in PTEN (ClinVar, Multiple submitters, 5 submitters; last evaluated 2023-01-12). Absent from gnomAD v4.1; Associated with PTEN hamartoma tumor syndrome.

What condition is associated with PTEN c.209+2T>C?

PTEN c.209+2T>C is associated with PTEN hamartoma tumor syndrome, Cowden syndrome 1, familial meningioma (ClinVar).

How common is PTEN c.209+2T>C in the general population?

PTEN c.209+2T>C is absent from gnomAD v4.1 (gnomAD).

How is PTEN hamartoma tumor syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

PTEN c.209+2T>C

rs878853937 · VCV584751

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

PTEN hamartoma tumor syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	Δ0.99	donor loss · deltas
Pangolin	Δ0.86	loss · gain 0.73 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.9	GERP 2.6, phastCons 1
Non-coding constraint	Z 1.63	1 kb window · o/e 0.87 · regional · uncalibrated
Overall
CADD	34.0	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

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
Coding: c.209+2T>C
MANE Select: NM_000314
dbSNP: rs878853937
Type: single nucleotide variant
Location: chr10:87925559 (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

PTEN hamartoma tumor syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Cowden syndrome 1 familial meningioma

For PTEN hamartoma tumor syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

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
PTEN c.209+5G>C Likely pathogenic ★★★ same condition
PTEN c.492+1G>T 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-c-209-plus-2t-c (accessed [today's date]).

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