Is PTEN p.Arg15Ser (c.45A>T) pathogenic?

PTEN p.Arg15Ser (c.45A>T) is classified Pathogenic/Likely pathogenic in PTEN (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-05-14). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with PTEN p.Arg15Ser (c.45A>T)?

PTEN p.Arg15Ser (c.45A>T) is associated with hereditary neoplastic syndrome, Cowden syndrome 1, PTEN hamartoma tumor syndrome (ClinVar).

How common is PTEN p.Arg15Ser (c.45A>T) in the general population?

PTEN p.Arg15Ser (c.45A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PTEN p.Arg15Ser (c.45A>T)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

PTEN p.Arg15Ser

c.45A>T · rs1064794096 · VCV419769

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic ✓ concordant with ClinVar · top 8% in PTEN
REVEL	0.799	moderately pathogenic-leaning
SaProt	LLR -15.39	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.70 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.1	GERP 0.64, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 69 kb · p 6.5e-17 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Arg15Ser
Coding: c.45A>T
MANE Select: NM_000314
dbSNP: rs1064794096
Type: single nucleotide variant
Location: chr10:87864514 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 15: the phosphatase tensin-type domain; a UniProt-annotated variant site (in cws1; also found in glioma)

Full PTEN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Also linked: Cowden syndrome 1 PTEN hamartoma tumor syndrome

Similar variants

PTEN p.Arg15Lys Likely pathogenic ★★★ same residue
PTEN p.Arg15Thr Likely pathogenic ★★★ same residue
PTEN p.Arg15Ile Likely pathogenic ★★ same residue
PTEN p.Arg15Ter Pathogenic ★★ same residue
PTEN p.Arg15Gly Likely pathogenic ★ same residue
PTEN p.Arg15= Benign ★ same residue
PTEN p.Arg15del Uncertain significance ★★★ same residue
PTEN p.Arg15fs Pathogenic ★★ same residue

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-arg15ser (accessed [today's date]).

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