Is PTPRS p.Pro1024Arg (c.3071C>G) pathogenic?

PTPRS p.Pro1024Arg (c.3071C>G) is classified Uncertain significance in PTPRS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-18). AlphaMissense: likely benign (0.16); Very rare (popmax 0.00535%, afr).

How common is PTPRS p.Pro1024Arg (c.3071C>G) in the general population?

PTPRS p.Pro1024Arg (c.3071C>G) is very rare (popmax 0.00535%, afr) (gnomAD).

What do computational predictors say about PTPRS p.Pro1024Arg (c.3071C>G)?

AlphaMissense predicts likely benign (score 0.16) — an in-silico prediction, not a clinical call.

PTPRS p.Pro1024Arg

c.3071C>G · rs772912033 · VCV3149596

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.16 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00535%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.16	likely benign
REVEL	0.316	indeterminate
SaProt	LLR -10.60	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -3.5, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 1,149 bp · p 0.12 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00535% African / African-American · 4/74,734 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00201% 32/1,595,648 alleles · very rare exomes 28/1,443,338 · genomes 4/152,310 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00535%	18,683
European (non-Finnish)	0.00212%	47,080
Finnishnot grpmax-eligible	0.00197%	50,780
Remaining individualsnot grpmax-eligible	0.00161%	62,036
South Asian	0.0011%	90,722

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.Pro1024Arg
Coding: c.3071C>G
MANE Select: NM_002850
dbSNP: rs772912033
Type: single nucleotide variant
Location: chr19:5222721 (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

Similar variants

PTPRS p.Pro1024Ala Uncertain significance ★ ⚠ same residue
PTPRS p.Pro1024Ser Uncertain significance ★ ⚠ same residue
PTPRS p.Pro1024Thr Uncertain significance ★ ⚠ same residue
PTPRS p.Pro1024= Likely benign same residue
PTPRS p.Arg1572Trp Uncertain significance ★★ ⚠ same type
PTPRS p.Ala87= Benign ★★ same type
PTPRS p.Ala972= Benign ★★ same type
PTPRS p.Asn1737= Benign ★★ 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/ptprs-p-pro1024arg (accessed [today's date]).

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