Is PTEN p.Cys296Arg (c.886T>C) pathogenic?

PTEN p.Cys296Arg (c.886T>C) is classified Uncertain significance in PTEN (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.113); Absent from gnomAD v4.1; Associated with Cowden syndrome 1.

What condition is associated with PTEN p.Cys296Arg (c.886T>C)?

PTEN p.Cys296Arg (c.886T>C) is associated with Cowden syndrome 1, macrocephaly-autism syndrome, familial meningioma (ClinVar).

How common is PTEN p.Cys296Arg (c.886T>C) in the general population?

PTEN p.Cys296Arg (c.886T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PTEN p.Cys296Arg (c.886T>C)?

AlphaMissense predicts likely benign (score 0.113) — an in-silico prediction, not a clinical call.

PTEN p.Cys296Arg

c.886T>C · rs786202207 · VCV185480

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.113 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cowden syndrome 1

Computational evidence

Protein change
AlphaMissense	0.113	likely benign
REVEL	0.334	indeterminate
SaProt	LLR -5.14	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 2.4, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 32 kb · p 4.1e-17 · regional, not allelic
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Cys296Arg
Coding: c.886T>C
MANE Select: NM_000314
dbSNP: rs786202207
Type: single nucleotide variant
Location: chr10:87960978 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 296: 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

Also linked: macrocephaly-autism syndrome familial meningioma glioma susceptibility 2 hereditary neoplastic syndrome PTEN hamartoma tumor syndrome prostate cancer, hereditary

Similar variants

PTEN p.Cys296Ter Pathogenic/Likely pathogenic ★★ same residue
PTEN p.Cys296Trp Uncertain significance ★★ ⚠ same residue
PTEN p.Cys296Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
PTEN p.Cys296_Asp297delinsTer Pathogenic ★ same residue
PTEN p.Cys296fs 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

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-cys296arg (accessed [today's date]).

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