PTEN p.Val351fs
c.1050dup · VCV3777125
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
2
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 | escapes | premature termination codon in the last exon (9 of 9) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2.9, phastCons 1 |
| Region caveats | ||
| Repeat context | seg dup | · reads may not map uniquely · confidence, not pathogenicity |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- PTEN
- Protein
- p.Val351fs
- Coding
- c.1050dup
- MANE Select
- NM_000314
- Type
- Duplication
- Location
- chr10:87965309 (GRCh38)
- Gene constraint
- LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 83.76 · 12 PDB
- Residue 351
- a UniProt-annotated variant site (in mcephas)
Disease context
macrocephaly-autism syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: Cowden syndrome 1
For Macrocephaly-intellectual disability-autism syndrome (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- Infancy, Neonatal
Similar variants
- PTEN p.Arg172fs Pathogenic ★★★ same condition
- PTEN p.Val351del Uncertain significance ★★★ same residue
- PTEN c.254-30dup Benign ★★★ same condition
- PTEN c.253+1dup Pathogenic/Likely pathogenic ★★ same condition
- PTEN p.Ala148fs Pathogenic ★★ same condition
- PTEN p.Asn292fs Pathogenic ★★ same condition
- PTEN p.Asp268fs Pathogenic ★★ same condition
- PTEN p.Gln149delinsLeuTer 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-val351fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown