Is PTEN p.Ala3Val (c.8C>T) pathogenic?

PTEN p.Ala3Val (c.8C>T) is classified Uncertain significance in PTEN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-18). AlphaMissense: ambiguous (0.486); Absent from gnomAD v4.1; Associated with PTEN hamartoma tumor syndrome.

What condition is associated with PTEN p.Ala3Val (c.8C>T)?

PTEN p.Ala3Val (c.8C>T) is associated with PTEN hamartoma tumor syndrome, hereditary neoplastic syndrome (ClinVar).

How common is PTEN p.Ala3Val (c.8C>T) in the general population?

PTEN p.Ala3Val (c.8C>T) is absent from gnomAD v4.1 (gnomAD).

How is PTEN hamartoma tumor syndrome inherited?

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

What do computational predictors say about PTEN p.Ala3Val (c.8C>T)?

AlphaMissense predicts ambiguous (score 0.486) — an in-silico prediction, not a clinical call.

PTEN p.Ala3Val

c.8C>T · rs1564801650 · VCV629265

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.486 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

PTEN hamartoma tumor syndrome

Computational evidence

Protein change
AlphaMissense	0.486	ambiguous
REVEL	0.534	indeterminate
SaProt	LLR -5.02	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 69 kb · p 6.5e-17 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PTEN
Protein: p.Ala3Val
Coding: c.8C>T
MANE Select: NM_000314
dbSNP: rs1564801650
Type: single nucleotide variant
Location: chr10:87864477 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB

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

Disease context

PTEN hamartoma tumor syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For PTEN hamartoma tumor syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

PTEN p.Ala3Thr Uncertain significance ★★ ⚠ same residue
PTEN p.Ala3= Likely benign ★★ same residue
PTEN p.Ala3Asp Uncertain significance ★ ⚠ same residue
PTEN c.1026+1G>A Pathogenic ★★★ same condition
PTEN c.1027-1852A>G Likely pathogenic ★★★ same condition
PTEN c.1027-1G>A Pathogenic ★★★ same condition
PTEN c.165-1G>A Likely pathogenic ★★★ same condition
PTEN c.165-1G>C 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-ala3val (accessed [today's date]).

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