Is PTEN p.Glu285= (c.855A>G) pathogenic?

PTEN p.Glu285= (c.855A>G) is classified Benign/Likely benign in PTEN (ClinVar, Multiple submitters, 15 submitters; last evaluated 2026-02-01). Very rare (popmax 0.00229%, nfe); Associated with Breast and/or ovarian cancer.

What condition is associated with PTEN p.Glu285= (c.855A>G)?

PTEN p.Glu285= (c.855A>G) is associated with Breast and/or ovarian cancer, Cowden syndrome 1, hereditary neoplastic syndrome (ClinVar).

How common is PTEN p.Glu285= (c.855A>G) in the general population?

PTEN p.Glu285= (c.855A>G) is very rare (popmax 0.00229%, nfe) (gnomAD).

PTEN p.Glu285=

c.855A>G · rs751888926 · VCV183799

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 15 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00229%, nfe)

Conditions

Breast and/or ovarian cancer

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 9.3	GERP 2.4, phastCons 1
Overall
CADD	11.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00229% European (non-Finnish) · 27/1,179,766 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00192% 31/1,613,352 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00229%	43,695
South Asian	0.0022%	45,536
Remaining individualsnot grpmax-eligible	0.0016%	62,454
African / African-American	0.00134%	74,810

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.Glu285=
Coding: c.855A>G
MANE Select: NM_000314
dbSNP: rs751888926
Type: single nucleotide variant
Location: chr10:87960947 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 285: 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

Breast and/or ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Cowden syndrome 1 hereditary neoplastic syndrome PTEN hamartoma tumor syndrome

Similar variants

PTEN p.Glu285Ter Pathogenic ★★ same residue
PTEN p.Glu285Asp Uncertain significance ★★ ⚠ same residue
PTEN p.Glu285Lys Uncertain significance ★★ ⚠ same residue
PTEN p.Glu285fs 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-glu285 (accessed [today's date]).

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