Is PTPRO p.His362Arg (c.1085A>G) pathogenic?

PTPRO p.His362Arg (c.1085A>G) is classified Uncertain significance in PTPRO (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-12). AlphaMissense: likely benign (0.0878); Ultra-rare (popmax 0.095%, nfe); Associated with nephrotic syndrome, type 6.

What condition is associated with PTPRO p.His362Arg (c.1085A>G)?

PTPRO p.His362Arg (c.1085A>G) is associated with nephrotic syndrome, type 6 (ClinVar).

How common is PTPRO p.His362Arg (c.1085A>G) in the general population?

PTPRO p.His362Arg (c.1085A>G) is ultra-rare (popmax 0.095%, nfe) (gnomAD).

What do computational predictors say about PTPRO p.His362Arg (c.1085A>G)?

AlphaMissense predicts likely benign (score 0.0878) — an in-silico prediction, not a clinical call.

PTPRO p.His362Arg

Q: How is Hereditary steroid-resistant nephrotic syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1085A>G · rs141042273 · VCV1517987

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0878 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.095%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nephrotic syndrome, type 6

Computational evidence

Protein change
AlphaMissense	0.0878	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -3.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 258 kb · p 0.015 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.095% European (non-Finnish) · 1,119/1,178,386 alleles

Filtering AF 0.0903% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0885%

Overall 0.0742% 1,196/1,612,348 alleles · ultra-rare exomes 1,127/1,460,030 · genomes 69/152,318 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.095%	1,053
Ashkenazi Jewishnot grpmax-eligible	0.0947%	1,056
Remaining individualsnot grpmax-eligible	0.0336%	2,973
Finnishnot grpmax-eligible	0.0281%	3,557
African / African-American	0.00667%	15,004
Admixed American	0.00666%	15,005
South Asian	0.0011%	91,022

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.His362Arg
Coding: c.1085A>G
MANE Select: NM_030667
dbSNP: rs141042273
Type: single nucleotide variant
Location: chr12:15502043 (GRCh38)
Gene constraint: LOEUF 0.513 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 77.55 · 2 PDB
Residue 362: the fibronectin type-iii 4 domain

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

Disease context

nephrotic syndrome, type 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary steroid-resistant nephrotic syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal

Similar variants

PTPRO p.His362Tyr Uncertain significance ★ ⚠ same residue
PTPRO p.Ala1086Val Uncertain significance ★★ ⚠ same condition
PTPRO p.Ala591Thr Uncertain significance ★★ ⚠ same condition
PTPRO p.Arg480Trp Uncertain significance ★★ same condition
PTPRO p.Arg607Gln Uncertain significance ★★ ⚠ same condition
PTPRO p.Asp162Val Uncertain significance ★★ ⚠ same condition
PTPRO p.Asp799Gly Uncertain significance ★★ ⚠ same condition
PTPRO p.Glu214Lys Uncertain significance ★★ ⚠ 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-his362arg (accessed [today's date]).

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