Is PTPRS p.Pro1024= (c.3072C>T) pathogenic?

PTPRS p.Pro1024= (c.3072C>T) is classified Likely benign in PTPRS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-17). Ultra-rare (popmax 0.0817%, afr); Associated with PTPRS-related disorder.

What condition is associated with PTPRS p.Pro1024= (c.3072C>T)?

PTPRS p.Pro1024= (c.3072C>T) is associated with PTPRS-related disorder (ClinVar).

How common is PTPRS p.Pro1024= (c.3072C>T) in the general population?

PTPRS p.Pro1024= (c.3072C>T) is ultra-rare (popmax 0.0817%, afr) (gnomAD).

PTPRS p.Pro1024=

c.3072C>T · rs550094738 · VCV3040729

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0817%, afr)

Conditions

PTPRS-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -3.5
Overall
CADD	6.532	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0817% African / African-American · 61/74,622 alleles

Filtering AF 0.0652% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0593%

Overall 0.0103% 164/1,594,238 alleles · ultra-rare exomes 117/1,441,964 · genomes 47/152,274 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0817%	1,223
Remaining individualsnot grpmax-eligible	0.0194%	5,164
East Asian	0.0135%	7,420
South Asian	0.0121%	8,239
European (non-Finnish)	0.00604%	16,570
Finnishnot grpmax-eligible	0.00395%	25,303
Admixed American	0.00169%	59,262

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.Pro1024=
Coding: c.3072C>T
MANE Select: NM_002850
dbSNP: rs550094738
Type: single nucleotide variant
Location: chr19:5222720 (GRCh38)
Gene constraint: LOEUF 0.378 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.94 · 6 PDB
Residue 1024: the fibronectin type-iii 7 domain

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

Disease context

PTPRS-related disorder

Similar variants

PTPRS p.Pro1024Ala Uncertain significance ★ ⚠ same residue
PTPRS p.Pro1024Arg Uncertain significance ★ ⚠ same residue
PTPRS p.Pro1024Ser Uncertain significance ★ ⚠ same residue
PTPRS p.Pro1024Thr 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

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-pro1024 (accessed [today's date]).

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