Is PTEN p.Val290Lysfs (c.866_867insGA) pathogenic?

PTEN p.Val290Lysfs (c.866867insGA) is classified Likely pathogenic in PTEN (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-18). Absent from gnomAD; Associated with macrocephaly-autism syndrome.

What condition is associated with PTEN p.Val290Lysfs (c.866_867insGA)?

PTEN p.Val290Lysfs (c.866_867insGA) is associated with macrocephaly-autism syndrome (ClinVar).

How common is PTEN p.Val290Lysfs (c.866_867insGA) in the general population?

PTEN p.Val290Lysfs (c.866_867insGA) is absent from gnomAD (gnomAD).

PTEN p.Val290Lysfs

Q: How is Macrocephaly-intellectual disability-autism syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.866_867insGA · rs1564568303 · VCV560715

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

macrocephaly-autism 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	predicted	premature termination codon in exon 8 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.3	GERP 1.3, 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.Val290Lysfs
Coding: c.866_867insGA
MANE Select: NM_000314
dbSNP: rs1564568303
Type: Insertion
Location: chr10:87960957 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 290: the c2 tensin-type domain; a UniProt-annotated variant site (in mcephas); a UniProt-annotated variant site (in)

Full PTEN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

macrocephaly-autism syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Macrocephaly-intellectual disability-autism syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

Similar variants

PTEN p.Val290fs Pathogenic ★★ same residue
PTEN p.Val290Ala Uncertain significance ★★ ⚠ same residue
PTEN p.Leu146fs Pathogenic ★ same condition
PTEN p.Val290Ile Uncertain significance ★ ⚠ same residue
PTEN p.Val290Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
PTEN p.Val290= Likely benign ★ same residue
PTEN c.634+2T>C Pathogenic ★★★ same condition
PTEN c.634+5G>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-val290lysfs (accessed [today's date]).

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