Is PTPRS p.Ala620= (c.1860C>G) pathogenic?

PTPRS p.Ala620= (c.1860C>G) is classified Likely benign in PTPRS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-17). Ultra-rare (popmax 0.0267%, mid); Associated with PTPRS-related disorder.

What condition is associated with PTPRS p.Ala620= (c.1860C>G)?

PTPRS p.Ala620= (c.1860C>G) is associated with PTPRS-related disorder (ClinVar).

How common is PTPRS p.Ala620= (c.1860C>G) in the general population?

PTPRS p.Ala620= (c.1860C>G) is ultra-rare (popmax 0.0267%, mid) (gnomAD).

PTPRS p.Ala620=

c.1860C>G · rs751470276 · VCV3033378

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, mid)

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 4.8	GERP -1.1, phastCons 1
Overall
CADD	12.61	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% Middle Eastern · 1/3,748 alleles

Filtering AF 0.0142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.011%

Overall 0.00358% 50/1,396,682 alleles · ultra-rare exomes 38/1,268,338 · genomes 12/128,344 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0267%	3,748
Admixed American	0.0255%	3,919
Remaining individualsnot grpmax-eligible	0.00958%	10,438
European (non-Finnish)	0.00302%	33,099
South Asian	0.00136%	73,444

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.Ala620=
Coding: c.1860C>G
MANE Select: NM_002850
dbSNP: rs751470276
Type: single nucleotide variant
Location: chr19:5231605 (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-ala620 (accessed [today's date]).

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