Is PTPRB p.Pro1564Ser (c.4690C>T) pathogenic?

PTPRB p.Pro1564Ser (c.4690C>T) is classified Uncertain significance in PTPRB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-02). Very rare (popmax 0.00329%, sas).

How common is PTPRB p.Pro1564Ser (c.4690C>T) in the general population?

PTPRB p.Pro1564Ser (c.4690C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

PTPRB p.Pro1564Ser

c.4690C>T · VCV3311498

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.1	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 10	GERP 1.7, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 18 kb · p 1.1e-09 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,070 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.00031% 5/1,613,522 alleles · very rare exomes 4/1,461,372 · genomes 1/152,150 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,357
Remaining individualsnot grpmax-eligible	0.0016%	62,448
African / African-American	0.00134%	74,898

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.Pro1564Ser
Coding: c.4690C>T
MANE Select: NM_001109754
Type: single nucleotide variant
Location: chr12:70559367 (GRCh38)

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

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-pro1564ser (accessed [today's date]).

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