Is PTPRO p.Arg607Gln (c.1820G>A) pathogenic?

PTPRO p.Arg607Gln (c.1820G>A) is classified Uncertain significance in PTPRO (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-09). AlphaMissense: likely benign (0.3236); Very rare (popmax 0.000424%, nfe); Associated with nephrotic syndrome, type 6.

What condition is associated with PTPRO p.Arg607Gln (c.1820G>A)?

PTPRO p.Arg607Gln (c.1820G>A) is associated with nephrotic syndrome, type 6 (ClinVar).

How common is PTPRO p.Arg607Gln (c.1820G>A) in the general population?

PTPRO p.Arg607Gln (c.1820G>A) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about PTPRO p.Arg607Gln (c.1820G>A)?

AlphaMissense predicts likely benign (score 0.3236) — an in-silico prediction, not a clinical call.

PTPRO p.Arg607Gln

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.1820G>A · VCV3428211

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3236 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

nephrotic syndrome, type 6

Computational evidence

Protein change
AlphaMissense	0.3236	likely benign
REVEL	0.396	indeterminate
SaProt	LLR -7.83	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 258 kb · p 0.015 · regional, not allelic
Overall
CADD	32.0	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 0.000424% European (non-Finnish) · 5/1,179,854 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,613,778 alleles · very rare exomes 6/1,461,636 · genomes 0/152,142 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00156%	64,004
European (non-Finnish)grpmax	0.000424%	235,971

Finnish 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.Arg607Gln
Coding: c.1820G>A
MANE Select: NM_030667
Type: single nucleotide variant
Location: chr12:15520241 (GRCh38)
Gene constraint: LOEUF 0.513 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 77.55 · 2 PDB
Residue 607: the fibronectin type-iii 6 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.Ala1086Val Uncertain significance ★★ ⚠ same condition
PTPRO p.Ala591Thr Uncertain significance ★★ ⚠ same condition
PTPRO p.Arg480Trp 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
PTPRO p.Glu564Lys Uncertain significance ★★ ⚠ same condition
PTPRO p.Glu70Lys 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-arg607gln (accessed [today's date]).

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