Is PTEN p.Ile306Val (c.916A>G) pathogenic?

PTEN p.Ile306Val (c.916A>G) is classified Uncertain significance in PTEN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-14). AlphaMissense: likely benign (0.0555); Very rare (popmax 0.0011%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with PTEN p.Ile306Val (c.916A>G)?

PTEN p.Ile306Val (c.916A>G) is associated with hereditary neoplastic syndrome, PTEN hamartoma tumor syndrome (ClinVar).

How common is PTEN p.Ile306Val (c.916A>G) in the general population?

PTEN p.Ile306Val (c.916A>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about PTEN p.Ile306Val (c.916A>G)?

AlphaMissense predicts likely benign (score 0.0555) — an in-silico prediction, not a clinical call.

PTEN p.Ile306Val

c.916A>G · rs786203858 · VCV187604

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0555 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0555	likely benign
REVEL	0.221	benign-leaning
SaProt	LLR -5.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 32 kb · p 4.1e-17 · regional, not allelic
Overall
CADD	20.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,076 alleles

Overall 0.000137% 2/1,461,648 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,076
European (non-Finnish)	8.48e-05%	1,179,884

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PTEN
Protein: p.Ile306Val
Coding: c.916A>G
MANE Select: NM_000314
dbSNP: rs786203858
Type: single nucleotide variant
Location: chr10:87961008 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 306: 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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: PTEN hamartoma tumor syndrome

Similar variants

PTEN p.Ile306Met Uncertain significance ★★ ⚠ same residue
PTEN p.Ile306Thr 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
PTEN c.209+4A>G 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-ile306val (accessed [today's date]).

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