Is PTPRO p.Asp1074= (c.3222C>T) pathogenic?

PTPRO p.Asp1074= (c.3222C>T) is classified Benign/Likely benign in PTPRO (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-23). Rare (popmax 0.392%, afr); Associated with nephrotic syndrome, type 6.

What condition is associated with PTPRO p.Asp1074= (c.3222C>T)?

PTPRO p.Asp1074= (c.3222C>T) is associated with nephrotic syndrome, type 6 (ClinVar).

How common is PTPRO p.Asp1074= (c.3222C>T) in the general population?

PTPRO p.Asp1074= (c.3222C>T) is rare (popmax 0.392%, afr) (gnomAD).

PTPRO p.Asp1074=

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.3222C>T · rs144347297 · VCV737213

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.392%, afr)

Conditions

nephrotic syndrome, type 6

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 -5.7
Overall
CADD	0.322	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.392% African / African-American · 294/75,006 alleles

Filtering AF 0.355% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.341%

Overall 0.0269% 434/1,613,976 alleles · rare exomes 196/1,461,730 · genomes 238/152,246 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.392%	255
Admixed American	0.137%	732
Remaining individualsnot grpmax-eligible	0.0608%	1,645
Middle Eastern	0.033%	3,030
South Asian	0.00439%	22,772
East Asian	0.00223%	44,834
European (non-Finnish)	0.0011%	90,765

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.Asp1074=
Coding: c.3222C>T
MANE Select: NM_030667
dbSNP: rs144347297
Type: single nucleotide variant
Location: chr12:15581768 (GRCh38)
Gene constraint: LOEUF 0.513 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 77.55 · 2 PDB
Residue 1074: the tyrosine-protein phosphatase domain; a β-strand

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.Asp1074Glu Benign/Likely benign ★★ 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-asp1074 (accessed [today's date]).

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