Is PTPRB p.Pro1728Arg (c.5183C>G) pathogenic?

PTPRB p.Pro1728Arg (c.5183C>G) is classified Uncertain significance in PTPRB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). Very rare (popmax 0.00167%, amr).

How common is PTPRB p.Pro1728Arg (c.5183C>G) in the general population?

PTPRB p.Pro1728Arg (c.5183C>G) is very rare (popmax 0.00167%, amr) (gnomAD).

PTPRB p.Pro1728Arg

c.5183C>G · VCV4836339

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.52	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 18 kb · p 1.1e-09 · regional, not allelic
Overall
CADD	27.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,018 alleles

Overall 6.2e-05% 1/1,613,810 alleles · very rare exomes 1/1,461,478 · genomes 0/152,332 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PTPRB
Protein: p.Pro1728Arg
Coding: c.5183C>G
MANE Select: NM_001109754
Type: single nucleotide variant
Location: chr12:70552981 (GRCh38)
Gene constraint: LOEUF 0.466 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.67 · 14 PDB
Residue 1728: the tyrosine-protein phosphatase domain; an α-helix

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

Similar variants

PTPRB c.3370+4A>G Benign ★★ same type
PTPRB p.Ala1520= Benign ★★ same type
PTPRB p.Leu1142= Benign ★★ same type
PTPRB p.Pro1816= Benign/Likely benign ★★ same type
PTPRB p.Thr1699= Benign ★★ same type
PTPRB p.Ala1027Ser Uncertain significance ★ same type
PTPRB p.Ala1088Thr Uncertain significance ★ same type
PTPRB p.Ala1117Val 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/ptprb-p-pro1728arg (accessed [today's date]).

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