Is PTEN p.Arg335fs (c.1004_1008del) pathogenic?

PTEN p.Arg335fs (c.10041008del) is classified Likely pathogenic in PTEN (ClinVar, Single submitter, 1 submitter; last evaluated 2020-06-23). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with PTEN p.Arg335fs (c.1004_1008del)?

PTEN p.Arg335fs (c.1004_1008del) is associated with hereditary neoplastic syndrome (ClinVar).

How common is PTEN p.Arg335fs (c.1004_1008del) in the general population?

PTEN p.Arg335fs (c.1004_1008del) is absent from gnomAD (gnomAD).

PTEN p.Arg335fs

c.1004_1008del · rs2493777058 · VCV1776639

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (8 of 9, 23 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.2	GERP 0.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PTEN
Protein: p.Arg335fs
Coding: c.1004_1008del
MANE Select: NM_000314
dbSNP: rs2493777058
Type: Deletion
Location: chr10:87961095 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 335: a β-strand; 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

Similar variants

PTEN p.Arg335Ter Pathogenic ★★★ same residue
PTEN p.Arg335Gln Uncertain significance ★★★ ⚠ same residue
PTEN p.Arg335= Conflicting classifications of pathogenicity ★ same residue
PTEN p.Arg335_Asn340del Uncertain significance ★ same residue
PTEN c.209+4_209+7del Pathogenic ★★★ same condition
PTEN c.801+1del Pathogenic ★★★ same condition
PTEN p.Asn329fs Pathogenic ★★★ same condition
PTEN p.Gln17fs 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-arg335fs (accessed [today's date]).

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