Is PTEN p.His64Gln (c.192T>G) pathogenic?

PTEN p.His64Gln (c.192T>G) is classified Uncertain significance in PTEN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-31). AlphaMissense: ambiguous (0.5419); Absent from gnomAD v4.1; Associated with glioma susceptibility 2.

What condition is associated with PTEN p.His64Gln (c.192T>G)?

PTEN p.His64Gln (c.192T>G) is associated with glioma susceptibility 2 (ClinVar).

How common is PTEN p.His64Gln (c.192T>G) in the general population?

PTEN p.His64Gln (c.192T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PTEN p.His64Gln (c.192T>G)?

AlphaMissense predicts ambiguous (score 0.5419) — an in-silico prediction, not a clinical call.

PTEN p.His64Gln

c.192T>G · rs2132232280 · VCV3240232

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5419 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

glioma susceptibility 2

Computational evidence

Protein change
AlphaMissense	0.5419	ambiguous
REVEL	0.811	moderately pathogenic-leaning
SaProt	LLR -10.45	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.8, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 69 kb · p 6.5e-17 · regional, not allelic
Overall
CADD	26.8	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.His64Gln
Coding: c.192T>G
MANE Select: NM_000314
dbSNP: rs2132232280
Type: single nucleotide variant
Location: chr10:87925540 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 12 PDB
Residue 64: the phosphatase tensin-type domain

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

Disease context

glioma susceptibility 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PTEN p.His64Pro Pathogenic/Likely pathogenic ★★ same residue
PTEN p.His64Arg Uncertain significance ★★ ⚠ same residue
PTEN p.His64Tyr Uncertain significance ★★ ⚠ same residue
PTEN p.His64Asn Uncertain significance ★ ⚠ same residue
PTEN p.His64Asp Uncertain significance ★ ⚠ same residue
PTEN c.634+2T>C Pathogenic ★★★ same condition
PTEN c.634+5G>A Pathogenic ★★★ same condition
PTEN p.Arg173Cys 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-his64gln (accessed [today's date]).

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