Is PTPRE p.Pro284= (c.852C>T) pathogenic?

PTPRE p.Pro284= (c.852C>T) is classified Likely benign in PTPRE (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-01). Ultra-rare (popmax 0.0154%, sas).

How common is PTPRE p.Pro284= (c.852C>T) in the general population?

PTPRE p.Pro284= (c.852C>T) is ultra-rare (popmax 0.0154%, sas) (gnomAD).

PTPRE p.Pro284=

c.852C>T · rs372533990 · VCV2640962

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0154%, sas)

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 -2.5
Overall
CADD	0.117	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0154% South Asian · 14/90,958 alleles

Filtering AF 0.00921% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00736%

Overall 0.0018% 29/1,612,270 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0154%	6,497
Admixed American	0.00334%	29,936
Remaining individualsnot grpmax-eligible	0.0016%	62,394
European (non-Finnish)	0.00102%	98,253

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: PTPRE
Protein: p.Pro284=
Coding: c.852C>T
MANE Select: NM_006504
dbSNP: rs372533990
Type: single nucleotide variant
Location: chr10:128068131 (GRCh38)
Gene constraint: LOEUF 0.635 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.42 · 4 PDB
Residue 284: the tyrosine-protein phosphatase 1 domain

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

Similar variants

PTPRE p.Ala129Thr Uncertain significance ★ ⚠ same type
PTPRE p.Ala289Val Uncertain significance ★ ⚠ same type
PTPRE p.Ala328Ser Uncertain significance ★ ⚠ same type
PTPRE p.Ala578Thr Uncertain significance ★ ⚠ same type
PTPRE p.Ala602Thr Uncertain significance ★ ⚠ same type
PTPRE p.Ala65Val Uncertain significance ★ ⚠ same type
PTPRE p.Ala66Thr Uncertain significance ★ ⚠ same type
PTPRE p.Arg125His Uncertain significance ★ ⚠ 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/ptpre-p-pro284 (accessed [today's date]).

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