Is PTPRB p.Arg552Ser (c.1656A>C) pathogenic?

PTPRB p.Arg552Ser (c.1656A>C) is classified Uncertain significance in PTPRB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-16). Very rare (popmax 0.00167%, amr).

How common is PTPRB p.Arg552Ser (c.1656A>C) in the general population?

PTPRB p.Arg552Ser (c.1656A>C) is very rare (popmax 0.00167%, amr) (gnomAD).

PTPRB p.Arg552Ser

c.1656A>C · VCV4147681

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	0.111	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP 0.59, phastCons 0.38
Regional constraint	o/e 0.94	unconstrained · MANE · 66 kb · p 0.021 · regional, not allelic
Overall
CADD	17.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,006 alleles

Overall 6.2e-05% 1/1,613,910 alleles · very rare exomes 1/1,461,582 · genomes 0/152,328 · 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.Arg552Ser
Coding: c.1656A>C
MANE Select: NM_001109754
Type: single nucleotide variant
Location: chr12:70592406 (GRCh38)
Gene constraint: LOEUF 0.466 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.67 · 14 PDB
Residue 552: the fibronectin type-iii 6 domain

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-arg552ser (accessed [today's date]).

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