Is PTPRS p.Pro1023Ser (c.3067C>T) pathogenic?

PTPRS p.Pro1023Ser (c.3067C>T) is classified Uncertain significance in PTPRS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-12). AlphaMissense: likely benign (0.2003); Ultra-rare (popmax 0.0496%, sas).

How common is PTPRS p.Pro1023Ser (c.3067C>T) in the general population?

PTPRS p.Pro1023Ser (c.3067C>T) is ultra-rare (popmax 0.0496%, sas) (gnomAD).

What do computational predictors say about PTPRS p.Pro1023Ser (c.3067C>T)?

AlphaMissense predicts likely benign (score 0.2003) — an in-silico prediction, not a clinical call.

PTPRS p.Pro1023Ser

c.3067C>T · rs752821383 · VCV2622697

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2003 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0496%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2003	likely benign
REVEL	0.451	indeterminate
SaProt	LLR -8.32	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 1.8, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 1,149 bp · p 0.12 · regional, not allelic
Overall
CADD	27.5	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 0.0496% South Asian · 45/90,778 alleles

Filtering AF 0.038% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.034%

Overall 0.00695% 111/1,596,092 alleles · ultra-rare exomes 103/1,443,880 · genomes 8/152,212 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0496%	2,017
Finnishnot grpmax-eligible	0.0138%	7,258
Remaining individualsnot grpmax-eligible	0.00806%	12,410
East Asian	0.00448%	22,327
European (non-Finnish)	0.00425%	23,546
Admixed American	0.00168%	59,534
African / African-American	0.00134%	74,638

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.Pro1023Ser
Coding: c.3067C>T
MANE Select: NM_002850
dbSNP: rs752821383
Type: single nucleotide variant
Location: chr19:5222725 (GRCh38)
Gene constraint: LOEUF 0.378 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.94 · 6 PDB
Residue 1023: the fibronectin type-iii 7 domain

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

Similar variants

PTPRS p.Pro1023Thr Uncertain significance ★ ⚠ 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
PTPRS p.Glu165= Likely benign ★★ same type
PTPRS p.Gly1107= Likely benign ★★ same type
PTPRS p.His1642= 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-pro1023ser (accessed [today's date]).

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