Is PTPRS p.Pro1024Ala (c.3070C>G) pathogenic?

PTPRS p.Pro1024Ala (c.3070C>G) is classified Uncertain significance in PTPRS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-01). AlphaMissense: likely benign (0.0594); Ultra-rare (popmax 0.0515%, eas).

How common is PTPRS p.Pro1024Ala (c.3070C>G) in the general population?

PTPRS p.Pro1024Ala (c.3070C>G) is ultra-rare (popmax 0.0515%, eas) (gnomAD).

What do computational predictors say about PTPRS p.Pro1024Ala (c.3070C>G)?

AlphaMissense predicts likely benign (score 0.0594) — an in-silico prediction, not a clinical call.

PTPRS p.Pro1024Ala

c.3070C>G · rs202163446 · VCV2229687

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0594 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0515%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0594	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -6.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -3.5, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 1,149 bp · p 0.12 · regional, not allelic
Overall
CADD	21.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0515% East Asian · 23/44,636 alleles

Filtering AF 0.0352% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0298%

Overall 0.00257% 41/1,595,558 alleles · ultra-rare exomes 39/1,443,354 · genomes 2/152,204 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0515%	1,941
South Asian	0.00441%	22,692
Admixed American	0.00168%	59,468
Remaining individualsnot grpmax-eligible	0.00161%	62,008
European (non-Finnish)	0.00102%	98,087

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.Pro1024Ala
Coding: c.3070C>G
MANE Select: NM_002850
dbSNP: rs202163446
Type: single nucleotide variant
Location: chr19:5222722 (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.Pro1024Arg 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-pro1024ala (accessed [today's date]).

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