Is PTEN p.Asp324= (c.972T>C) pathogenic?

PTEN p.Asp324= (c.972T>C) is classified Benign in PTEN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-13). Very rare (popmax 0.00223%, eas); Associated with Cowden syndrome 1.

What condition is associated with PTEN p.Asp324= (c.972T>C)?

PTEN p.Asp324= (c.972T>C) is associated with Cowden syndrome 1 (ClinVar).

How common is PTEN p.Asp324= (c.972T>C) in the general population?

PTEN p.Asp324= (c.972T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

PTEN p.Asp324=

c.972T>C · VCV3903751

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 3.5	GERP 2.6, phastCons 1
Overall
CADD	11.88	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,824 alleles

Overall 6.84e-05% 1/1,461,600 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.

Variant & gene context

Gene: PTEN
Protein: p.Asp324=
Coding: c.972T>C
MANE Select: NM_000314
Type: single nucleotide variant
Location: chr10:87961064 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 324: an α-helix; 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.Asp324Glu Uncertain significance ★★ ⚠ same residue
PTEN p.Asp324Gly Uncertain significance ★★ ⚠ 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
PTEN c.492+2T>G 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-asp324 (accessed [today's date]).

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