Is PTEN p.Ile122= (c.366T>C) pathogenic?

PTEN p.Ile122= (c.366T>C) is classified Likely benign in PTEN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-01). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with PTEN p.Ile122= (c.366T>C)?

PTEN p.Ile122= (c.366T>C) is associated with hereditary neoplastic syndrome, PTEN hamartoma tumor syndrome (ClinVar).

How common is PTEN p.Ile122= (c.366T>C) in the general population?

PTEN p.Ile122= (c.366T>C) is absent from gnomAD v4.1 (gnomAD).

PTEN p.Ile122=

c.366T>C · rs1564830125 · VCV628202

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP -0.17, phastCons 1
Overall
CADD	12.4	PHRED · no single calibrated threshold — expert panels disagree

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.Ile122=
Coding: c.366T>C
MANE Select: NM_000314
dbSNP: rs1564830125
Type: single nucleotide variant
Location: chr10:87933125 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 122: a β-strand; the phosphatase 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.Ile122Val Uncertain significance ★★★ ⚠ same residue
PTEN p.Ile122Met Uncertain significance ★ ⚠ same residue
PTEN p.Ile122Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
PTEN p.Ile122Thr Uncertain significance ★ ⚠ same residue
PTEN p.Ile122fs Pathogenic ★ same residue
PTEN p.Ile122Asn Uncertain significance ⚠ same residue
PTEN p.Ile122Leu Uncertain significance ⚠ same residue
PTEN c.1026+1G>A 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-ile122 (accessed [today's date]).

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