Is PTPRS p.Pro644= (c.1932G>A) pathogenic?

PTPRS p.Pro644= (c.1932G>A) is classified Likely benign in PTPRS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-12-03). Rare (popmax 0.117%, sas); Associated with PTPRS-related disorder.

What condition is associated with PTPRS p.Pro644= (c.1932G>A)?

PTPRS p.Pro644= (c.1932G>A) is associated with PTPRS-related disorder (ClinVar).

How common is PTPRS p.Pro644= (c.1932G>A) in the general population?

PTPRS p.Pro644= (c.1932G>A) is rare (popmax 0.117%, sas) (gnomAD).

PTPRS p.Pro644=

c.1932G>A · rs148862245 · VCV3048836

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.117%, sas)

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 -0.21	GERP -3.5, phastCons 0.45
Overall
CADD	16.59	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.117% South Asian · 106/90,912 alleles

Filtering AF 0.0985% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0918%

Overall 0.0126% 203/1,610,310 alleles · rare exomes 186/1,459,732 · genomes 17/150,578 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.117%	858
Middle Eastern	0.0665%	1,504
Remaining individualsnot grpmax-eligible	0.0144%	6,930
Admixed American	0.00838%	11,932
African / African-American	0.00806%	12,400
European (non-Finnish)	0.00611%	16,379
East Asian	0.00223%	44,760

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.Pro644=
Coding: c.1932G>A
MANE Select: NM_002850
dbSNP: rs148862245
Type: single nucleotide variant
Location: chr19:5231533 (GRCh38)
Gene constraint: LOEUF 0.378 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.94 · 6 PDB
Residue 644: the fibronectin type-iii 4 domain

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

Disease context

PTPRS-related disorder

Similar variants

PTPRS p.Pro644Ala Uncertain significance ★ ⚠ same residue
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

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-pro644 (accessed [today's date]).

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