Is PTPRO p.Ala221= (c.663C>A) pathogenic?

PTPRO p.Ala221= (c.663C>A) is classified Likely benign in PTPRO (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-09-03). Absent from gnomAD v4.1; Associated with PTPRO-related disorder.

What condition is associated with PTPRO p.Ala221= (c.663C>A)?

PTPRO p.Ala221= (c.663C>A) is associated with PTPRO-related disorder (ClinVar).

How common is PTPRO p.Ala221= (c.663C>A) in the general population?

PTPRO p.Ala221= (c.663C>A) is absent from gnomAD v4.1 (gnomAD).

PTPRO p.Ala221=

c.663C>A · rs140390981 · VCV3032894

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

PTPRO-related disorder

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 -0.35	GERP -5, phastCons 0.093
Overall
CADD	7.417	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PTPRO
Protein: p.Ala221=
Coding: c.663C>A
MANE Select: NM_030667
dbSNP: rs140390981
Type: single nucleotide variant
Location: chr12:15501621 (GRCh38)
Gene constraint: LOEUF 0.513 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 77.55 · 2 PDB

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

Disease context

PTPRO-related disorder

Similar variants

PTPRO c.76-67403G>A Uncertain significance ★ same condition
PTPRO p.Ala731Thr Uncertain significance ⚠ same condition
PTPRO p.Ile365Phe Uncertain significance ⚠ same condition
PTPRO c.1891+6G>T Likely benign same condition
PTPRO c.1891+8A>T Likely benign same condition
PTPRO c.2438-10A>C Likely benign same condition
PTPRO c.2748-10T>C Likely benign same condition
PTPRO c.3255+7C>T 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/ptpro-p-ala221 (accessed [today's date]).

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