Is PTPRO p.Lys85= (c.255G>A) pathogenic?

PTPRO p.Lys85= (c.255G>A) is classified Likely benign in PTPRO (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-07-18). Very rare (popmax 0.00441%, nfe); Associated with PTPRO-related disorder.

What condition is associated with PTPRO p.Lys85= (c.255G>A)?

PTPRO p.Lys85= (c.255G>A) is associated with PTPRO-related disorder (ClinVar).

How common is PTPRO p.Lys85= (c.255G>A) in the general population?

PTPRO p.Lys85= (c.255G>A) is very rare (popmax 0.00441%, nfe) (gnomAD).

PTPRO p.Lys85=

c.255G>A · rs143278258 · VCV3036572

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00441%, nfe)

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 2	GERP -1.4, phastCons 1
Overall
CADD	5.888	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00441% European (non-Finnish) · 52/1,179,786 alleles

Filtering AF 0.00342% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.00341% 55/1,613,736 alleles · very rare exomes 50/1,461,550 · genomes 5/152,186 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00441%	22,688
Remaining individualsnot grpmax-eligible	0.0032%	31,245
African / African-American	0.00133%	75,026

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: PTPRO
Protein: p.Lys85=
Coding: c.255G>A
MANE Select: NM_030667
dbSNP: rs143278258
Type: single nucleotide variant
Location: chr12:15484153 (GRCh38)
Gene constraint: LOEUF 0.513 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 77.55 · 2 PDB
Residue 85: the fibronectin type-iii 1 domain

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-lys85 (accessed [today's date]).

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