Is PTPRO p.Ala386= (c.1158A>C) pathogenic?

PTPRO p.Ala386= (c.1158A>C) is classified Likely benign in PTPRO (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-02-27). Very rare (popmax 0.0049%, nfe); Associated with PTPRO-related disorder.

What condition is associated with PTPRO p.Ala386= (c.1158A>C)?

PTPRO p.Ala386= (c.1158A>C) is associated with PTPRO-related disorder (ClinVar).

How common is PTPRO p.Ala386= (c.1158A>C) in the general population?

PTPRO p.Ala386= (c.1158A>C) is very rare (popmax 0.0049%, nfe) (gnomAD).

PTPRO p.Ala386=

c.1158A>C · rs200206218 · VCV3031660

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0049%, nfe)

Conditions

PTPRO-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 0.3	GERP -5.6, phastCons 0.057
Overall
CADD	6.385	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0049% European (non-Finnish) · 57/1,163,952 alleles

Filtering AF 0.00383% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00349%

Overall 0.00608% 97/1,596,134 alleles · very rare exomes 90/1,443,922 · genomes 7/152,212 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0323%	3,095
Finnishnot grpmax-eligible	0.0282%	3,548
European (non-Finnish)grpmax	0.0049%	20,420
East Asian	0.00447%	22,375

Remaining individuals 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: PTPRO
Protein: p.Ala386=
Coding: c.1158A>C
MANE Select: NM_030667
dbSNP: rs200206218
Type: single nucleotide variant
Location: chr12:15503960 (GRCh38)
Gene constraint: LOEUF 0.513 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 77.55 · 2 PDB
Residue 386: the fibronectin type-iii 4 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-ala386 (accessed [today's date]).

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