Is PTEN p.Ile4Ser (c.11T>G) pathogenic?

PTEN p.Ile4Ser (c.11T>G) is classified Uncertain significance in PTEN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-06). AlphaMissense: ambiguous (0.4729); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with PTEN p.Ile4Ser (c.11T>G)?

PTEN p.Ile4Ser (c.11T>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is PTEN p.Ile4Ser (c.11T>G) in the general population?

PTEN p.Ile4Ser (c.11T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PTEN p.Ile4Ser (c.11T>G)?

AlphaMissense predicts ambiguous (score 0.4729) — an in-silico prediction, not a clinical call.

PTEN p.Ile4Ser

c.11T>G · rs1858394571 · VCV922734

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4729 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.4729	ambiguous
REVEL	0.446	indeterminate
SaProt	LLR -11.90	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 69 kb · p 6.5e-17 · regional, not allelic
Overall
CADD	23.8	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.Ile4Ser
Coding: c.11T>G
MANE Select: NM_000314
dbSNP: rs1858394571
Type: single nucleotide variant
Location: chr10:87864480 (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

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

Similar variants

PTEN p.Ile4Val Uncertain significance ★★★ ⚠ same residue
PTEN p.Ile4Thr Uncertain significance ★★ ⚠ same residue
PTEN p.Ile4= Likely benign ★★ same residue
PTEN p.Ile4fs Pathogenic ★ 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

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-ile4ser (accessed [today's date]).

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