Is PTPRS p.Ser1127= (c.3381C>T) pathogenic?

PTPRS p.Ser1127= (c.3381C>T) is classified Likely benign in PTPRS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-06). Ultra-rare (popmax 0.0633%, amr); Associated with PTPRS-related disorder.

What condition is associated with PTPRS p.Ser1127= (c.3381C>T)?

PTPRS p.Ser1127= (c.3381C>T) is associated with PTPRS-related disorder (ClinVar).

How common is PTPRS p.Ser1127= (c.3381C>T) in the general population?

PTPRS p.Ser1127= (c.3381C>T) is ultra-rare (popmax 0.0633%, amr) (gnomAD).

PTPRS p.Ser1127=

c.3381C>T · rs113337498 · VCV3044442

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0633%, amr)

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 -1.2	GERP -1.9
Overall
CADD	9.028	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0633% Admixed American · 38/60,018 alleles

Filtering AF 0.0474% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0418%

Overall 0.0157% 253/1,613,908 alleles · ultra-rare exomes 214/1,461,608 · genomes 39/152,300 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0633%	1,579
Remaining individualsnot grpmax-eligible	0.0256%	3,907
European (non-Finnish)	0.0161%	6,211
East Asian	0.00891%	11,220
South Asian	0.00329%	30,357
African / African-American	0.00267%	37,519

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.Ser1127=
Coding: c.3381C>T
MANE Select: NM_002850
dbSNP: rs113337498
Type: single nucleotide variant
Location: chr19:5221074 (GRCh38)
Gene constraint: LOEUF 0.378 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.94 · 6 PDB

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

Disease context

PTPRS-related disorder

Similar variants

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
PTPRS c.2495-4G>A Likely benign 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-ser1127 (accessed [today's date]).

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