Is PTEN p.Val249= (c.747G>T) pathogenic?

PTEN p.Val249= (c.747G>T) is classified Benign in PTEN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-12). Absent from gnomAD v4.1; Associated with Cowden syndrome 1.

What condition is associated with PTEN p.Val249= (c.747G>T)?

PTEN p.Val249= (c.747G>T) is associated with Cowden syndrome 1 (ClinVar).

How common is PTEN p.Val249= (c.747G>T) in the general population?

PTEN p.Val249= (c.747G>T) is absent from gnomAD v4.1 (gnomAD).

PTEN p.Val249=

c.747G>T · VCV3904296

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cowden syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP -0.91, phastCons 1
Overall
CADD	8.36	PHRED · no single calibrated threshold — expert panels disagree

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
Protein: p.Val249=
Coding: c.747G>T
MANE Select: NM_000314
Type: single nucleotide variant
Location: chr10:87957965 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 249: 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

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

Similar variants

PTEN p.Val249Gly Likely pathogenic ★★ same residue
PTEN p.Val249Met Uncertain significance ★★ ⚠ same residue
PTEN p.Val249Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
PTEN c.1026+1G>A 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.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-p-val249 (accessed [today's date]).

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