Is PTPRS p.Pro599= (c.1797G>A) pathogenic?

PTPRS p.Pro599= (c.1797G>A) is classified Likely benign in PTPRS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-19). Ultra-rare (popmax 0.029%, eas); Associated with PTPRS-related disorder.

What condition is associated with PTPRS p.Pro599= (c.1797G>A)?

PTPRS p.Pro599= (c.1797G>A) is associated with PTPRS-related disorder (ClinVar).

How common is PTPRS p.Pro599= (c.1797G>A) in the general population?

PTPRS p.Pro599= (c.1797G>A) is ultra-rare (popmax 0.029%, eas) (gnomAD).

PTPRS p.Pro599=

c.1797G>A · rs200933180 · VCV3052630

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

Conditions

PTPRS-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -13	GERP -3.5
Overall
CADD	10.64	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.029% East Asian · 13/44,792 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00478% 77/1,612,504 alleles · ultra-rare exomes 57/1,460,198 · genomes 20/152,306 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.029%	3,446
Admixed American	0.015%	6,654
Remaining individualsnot grpmax-eligible	0.0048%	20,818
European (non-Finnish)	0.00424%	23,591
African / African-American	0.00133%	74,952
South Asian	0.0011%	90,970

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: PTPRS
Protein: p.Pro599=
Coding: c.1797G>A
MANE Select: NM_002850
dbSNP: rs200933180
Type: single nucleotide variant
Location: chr19:5238971 (GRCh38)
Gene constraint: LOEUF 0.378 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.94 · 6 PDB
Residue 599: the fibronectin type-iii 3 domain

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

Disease context

PTPRS-related disorder

Similar variants

PTPRS p.Leu995Phe Uncertain significance ★ ⚠ same condition
PTPRS p.Thr1892Lys Uncertain significance ★ ⚠ same condition
PTPRS p.Val13Ile Uncertain significance ★ ⚠ same condition
PTPRS p.Ala1129Gly Uncertain significance ⚠ same condition
PTPRS p.Gly1904= Uncertain significance same condition
PTPRS p.His1693Gln Uncertain significance ⚠ same condition
PTPRS p.Thr677Ala Uncertain significance ⚠ same condition
PTPRS c.2495-4G>A Likely benign same condition

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/ptprs-p-pro599 (accessed [today's date]).

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