Is PTEN p.Asn48= (c.144C>T) pathogenic?

PTEN p.Asn48= (c.144C>T) is classified Benign/Likely benign in PTEN (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-06-09). Very rare (popmax 0.00167%, amr); Associated with PTEN hamartoma tumor syndrome.

What condition is associated with PTEN p.Asn48= (c.144C>T)?

PTEN p.Asn48= (c.144C>T) is associated with PTEN hamartoma tumor syndrome, Cowden syndrome 1, hereditary neoplastic syndrome (ClinVar).

How common is PTEN p.Asn48= (c.144C>T) in the general population?

PTEN p.Asn48= (c.144C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

How is PTEN hamartoma tumor syndrome inherited?

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

PTEN p.Asn48=

c.144C>T · rs762518389 · VCV481024

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

PTEN hamartoma tumor syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.24	donor loss · deltas
Constraint at this position
Conservation	phyloP 4.8	GERP 2.4, phastCons 1
Overall
CADD	12.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,980 alleles

Overall 6.85e-05% 1/1,459,500 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.Asn48=
Coding: c.144C>T
MANE Select: NM_000314
dbSNP: rs762518389
Type: single nucleotide variant
Location: chr10:87894089 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 48: the phosphatase tensin-type domain

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 hereditary neoplastic syndrome

For PTEN hamartoma tumor syndrome (Orphanet):

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

Similar variants

PTEN p.Asn48Lys Pathogenic/Likely pathogenic ★★ same residue
PTEN p.Asn48Ser Pathogenic ★★ same residue
PTEN p.Asn48Asp Uncertain significance ★★ ⚠ same residue
PTEN p.Asn48fs Pathogenic ★ 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

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-asn48 (accessed [today's date]).

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