Is PTEN p.Pro244fs (c.731del) pathogenic?

PTEN p.Pro244fs (c.731del) is classified Pathogenic in PTEN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-04-24). Absent from gnomAD; Associated with macrocephaly-autism syndrome.

What condition is associated with PTEN p.Pro244fs (c.731del)?

PTEN p.Pro244fs (c.731del) is associated with macrocephaly-autism syndrome, Cowden syndrome 1, PTEN hamartoma tumor syndrome (ClinVar).

How common is PTEN p.Pro244fs (c.731del) in the general population?

PTEN p.Pro244fs (c.731del) is absent from gnomAD (gnomAD).

PTEN p.Pro244fs

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

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

c.731del · rs2493767037 · VCV2674416

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

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 7 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.5, 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.Pro244fs
Coding: c.731del
MANE Select: NM_000314
dbSNP: rs2493767037
Type: Deletion
Location: chr10:87957947 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 244: 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

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

Also linked: Cowden syndrome 1 PTEN hamartoma tumor syndrome

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

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

Similar variants

PTEN p.Pro244Leu Uncertain significance ★★ ⚠ same residue
PTEN p.Pro244= Benign/Likely benign ★★ same residue
PTEN c.209+4_209+7del Pathogenic ★★★ same condition
PTEN c.210-2_211del Pathogenic ★★★ same condition
PTEN c.801+1del Pathogenic ★★★ same condition
PTEN c.802-2del 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-pro244fs (accessed [today's date]).

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