Is PTEN p.Asp395= (c.1185T>C) pathogenic?

PTEN p.Asp395= (c.1185T>C) is classified Benign/Likely benign in PTEN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-13). Absent from gnomAD v4.1; Associated with Cowden syndrome 1.

What condition is associated with PTEN p.Asp395= (c.1185T>C)?

PTEN p.Asp395= (c.1185T>C) is associated with Cowden syndrome 1, PTEN hamartoma tumor syndrome (ClinVar).

How common is PTEN p.Asp395= (c.1185T>C) in the general population?

PTEN p.Asp395= (c.1185T>C) is absent from gnomAD v4.1 (gnomAD).

PTEN p.Asp395=

c.1185T>C · VCV3727242

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

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 6.2	GERP 1.6, phastCons 1
Overall
CADD	10.06	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.Asp395=
Coding: c.1185T>C
MANE Select: NM_000314
Type: single nucleotide variant
Location: chr10:87965445 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 395: a UniProt-annotated variant site (in mcephas); the 'disordered' region

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: PTEN hamartoma tumor syndrome

Similar variants

PTEN p.Asp395Tyr Uncertain significance ★ ⚠ same residue
PTEN p.Asp395Asn Uncertain significance ★ ⚠ same residue
PTEN p.Asp395Gly Uncertain significance ★ ⚠ 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
PTEN c.165-1G>C 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-asp395 (accessed [today's date]).

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