Is PTPRG p.Arg593Pro (c.1778G>C) pathogenic?

PTPRG p.Arg593Pro (c.1778G>C) is classified Uncertain significance in PTPRG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-08). AlphaMissense: ambiguous (0.3688); Absent from gnomAD v4.1.

How common is PTPRG p.Arg593Pro (c.1778G>C) in the general population?

PTPRG p.Arg593Pro (c.1778G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PTPRG p.Arg593Pro (c.1778G>C)?

AlphaMissense predicts ambiguous (score 0.3688) — an in-silico prediction, not a clinical call.

PTPRG p.Arg593Pro

c.1778G>C · VCV4147819

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3688 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3688	ambiguous
REVEL	0.151	moderately benign-leaning
SaProt	LLR -8.09	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 0.88, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 125 kb · p 0.77 · regional, not allelic
Overall
CADD	24.5	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: PTPRG
Protein: p.Arg593Pro
Coding: c.1778G>C
MANE Select: NM_002841
Type: single nucleotide variant
Location: chr3:62203573 (GRCh38)
Gene constraint: LOEUF 0.714 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.76 · 20 PDB
Residue 593: the 'disordered' region

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

Similar variants

PTPRG p.Ala614Thr Uncertain significance ★★ ⚠ same type
PTPRG p.Ile1333Thr Uncertain significance ★★ ⚠ same type
PTPRG p.Asn429= Likely benign ★★ same type
PTPRG p.His412= Benign ★★ same type
PTPRG p.Leu14= Benign ★★ same type
PTPRG p.Pro58= Benign ★★ same type
PTPRG p.Ala1062Thr Uncertain significance ★ ⚠ same type
PTPRG p.Ala1190Thr 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/ptprg-p-arg593pro (accessed [today's date]).

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