Is PTPRS p.Ala87= (c.261A>C) pathogenic?

PTPRS p.Ala87= (c.261A>C) is classified Benign in PTPRS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-09-27). Common (popmax 28.3%, mid) — too common for a highly-penetrant pathogenic allele.

PTPRS p.Ala87=

Q: How common is PTPRS p.Ala87= (c.261A>C) in the general population?

PTPRS p.Ala87= (c.261A>C) is common (popmax 28.3%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.261A>C · rs1141371 · VCV1263463

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 28.3%, mid) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.4
Overall
CADD	0.028	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 28.3% Middle Eastern · 1,715/6,062 alleles

Filtering AF 27.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 26.7%

Overall 20.8% 336,502/1,613,918 alleles · common exomes 303,685/1,461,810 · genomes 32,817/152,108 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	32.2%	3
Middle Easterngrpmax	28.3%	4
African / African-American	26.5%	4
European (non-Finnish)	22.2%	5
Remaining individualsnot grpmax-eligible	21.2%	5
Amishnot grpmax-eligible	16.9%	6
Finnishnot grpmax-eligible	15%	7
Admixed American	13.9%	7
South Asian	13%	8
East Asian	0.0824%	1,213

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala87=
Coding: c.261A>C
MANE Select: NM_002850
dbSNP: rs1141371
Type: single nucleotide variant
Location: chr19:5273560 (GRCh38)
Gene constraint: LOEUF 0.378 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.94 · 6 PDB
Residue 87: the ig-like c2-type 1 domain

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

Similar variants

PTPRS p.Arg1572Trp Uncertain significance ★★ ⚠ 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
PTPRS p.Ile1741= Benign ★★ same type
PTPRS p.Leu1170= 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-ala87 (accessed [today's date]).

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