Is PTPRO p.Pro818Leu (c.2453C>T) pathogenic?

PTPRO p.Pro818Leu (c.2453C>T) is classified Uncertain significance in PTPRO (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-31). AlphaMissense: ambiguous (0.3524); Absent from gnomAD v4.1.

How common is PTPRO p.Pro818Leu (c.2453C>T) in the general population?

PTPRO p.Pro818Leu (c.2453C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PTPRO p.Pro818Leu (c.2453C>T)?

AlphaMissense predicts ambiguous (score 0.3524) — an in-silico prediction, not a clinical call.

PTPRO p.Pro818Leu

c.2453C>T · VCV4915773

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3524 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3524	ambiguous
REVEL	0.352	indeterminate
SaProt	LLR -5.92	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.3	GERP 2.4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 258 kb · p 0.015 · regional, not allelic
Overall
CADD	24.0	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: PTPRO
Protein: p.Pro818Leu
Coding: c.2453C>T
MANE Select: NM_030667
Type: single nucleotide variant
Location: chr12:15551566 (GRCh38)
Gene constraint: LOEUF 0.513 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 77.55 · 2 PDB

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

Similar variants

PTPRO p.Ala1086Val Uncertain significance ★★ ⚠ same type
PTPRO p.Ala591Thr Uncertain significance ★★ ⚠ same type
PTPRO p.Arg480Trp Uncertain significance ★★ same type
PTPRO p.Arg607Gln Uncertain significance ★★ ⚠ same type
PTPRO p.Asn569Asp Uncertain significance ★★ ⚠ same type
PTPRO p.Asp162Val Uncertain significance ★★ ⚠ same type
PTPRO p.Asp301His Uncertain significance ★★ ⚠ same type
PTPRO p.Asp799Gly Uncertain significance ★★ ⚠ same type

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/ptpro-p-pro818leu (accessed [today's date]).

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