Is PTEN p.Ala86fs (c.255_262delinsC) pathogenic?

PTEN p.Ala86fs (c.255262delinsC) is classified Pathogenic in PTEN (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-23). Absent from gnomAD; Associated with hemimegalencephaly.

What condition is associated with PTEN p.Ala86fs (c.255_262delinsC)?

PTEN p.Ala86fs (c.255_262delinsC) is associated with hemimegalencephaly (ClinVar).

How common is PTEN p.Ala86fs (c.255_262delinsC) in the general population?

PTEN p.Ala86fs (c.255_262delinsC) is absent from gnomAD (gnomAD).

PTEN p.Ala86fs

c.255_262delinsC · rs2132241980 · VCV1048543

Pathogenic Single submitter

Classification

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

hemimegalencephaly

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	predicted	premature termination codon in exon 5 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, 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.Ala86fs
Coding: c.255_262delinsC
MANE Select: NM_000314
dbSNP: rs2132241980
Type: Indel
Location: chr10:87933014 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 86: a β-strand; the phosphatase 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

hemimegalencephaly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PTEN p.Ala86= Conflicting classifications of pathogenicity ★ same residue
PTEN p.Ala86Thr Uncertain significance ★ ⚠ same residue
PTEN p.Ala86Val Uncertain significance ★ ⚠ same residue
PTEN p.Asp371fs Pathogenic ★ same condition
PTEN p.Tyr178_Ser179delinsTer Pathogenic ★★★ same type
PTEN c.156_164+4delinsCAT Likely pathogenic ★★ same type
PTEN p.Asp326_Lys330delinsAlaTer Pathogenic/Likely pathogenic ★★ same type
PTEN p.Leu182_Lys183insTer Pathogenic ★★ same type

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-ala86fs (accessed [today's date]).

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