Is PTEN p.Ser302Arg (c.906C>G) pathogenic?

PTEN p.Ser302Arg (c.906C>G) is classified Uncertain significance in PTEN (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-04-02). AlphaMissense: ambiguous (0.3604); Very rare (popmax 0.00167%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with PTEN p.Ser302Arg (c.906C>G)?

PTEN p.Ser302Arg (c.906C>G) is associated with hereditary neoplastic syndrome, glioma susceptibility 2, PTEN hamartoma tumor syndrome (ClinVar).

How common is PTEN p.Ser302Arg (c.906C>G) in the general population?

PTEN p.Ser302Arg (c.906C>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about PTEN p.Ser302Arg (c.906C>G)?

AlphaMissense predicts ambiguous (score 0.3604) — an in-silico prediction, not a clinical call.

PTEN p.Ser302Arg

c.906C>G · rs876660906 · VCV234182

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.3604 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.3604	ambiguous
REVEL	0.231	benign-leaning
SaProt	LLR -6.58	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.44	GERP -2.3, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 32 kb · p 4.1e-17 · regional, not allelic
Overall
CADD	18.94	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

Grpmax group 0.00167% Admixed American · 1/59,952 alleles

Overall 6.84e-05% 1/1,461,590 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.Ser302Arg
Coding: c.906C>G
MANE Select: NM_000314
dbSNP: rs876660906
Type: single nucleotide variant
Location: chr10:87960998 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 302: 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

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

Also linked: glioma susceptibility 2 PTEN hamartoma tumor syndrome

Similar variants

PTEN p.Ser302Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
PTEN p.Ser302Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
PTEN p.Ser302= Benign ★ 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-ser302arg (accessed [today's date]).

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