Is PTPRO p.Ser1177Phe (c.3530C>T) pathogenic?

PTPRO p.Ser1177Phe (c.3530C>T) is classified Likely benign in PTPRO (ClinVar, Single submitter, 2 submitters; last evaluated 2024-12-18). AlphaMissense: likely pathogenic (0.9296); Rare (popmax 0.214%, eas); Associated with nephrotic syndrome, type 6.

What condition is associated with PTPRO p.Ser1177Phe (c.3530C>T)?

PTPRO p.Ser1177Phe (c.3530C>T) is associated with nephrotic syndrome, type 6 (ClinVar).

How common is PTPRO p.Ser1177Phe (c.3530C>T) in the general population?

PTPRO p.Ser1177Phe (c.3530C>T) is rare (popmax 0.214%, eas) (gnomAD).

What do computational predictors say about PTPRO p.Ser1177Phe (c.3530C>T)?

AlphaMissense predicts likely pathogenic (score 0.9296) — an in-silico prediction, not a clinical call.

PTPRO p.Ser1177Phe

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.3530C>T · rs200478856 · VCV3031850

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9296 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.214%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nephrotic syndrome, type 6

Computational evidence

Protein change
AlphaMissense	0.9296	likely pathogenic
REVEL	0.147	moderately benign-leaning
SaProt	LLR -7.71	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 0.95, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 14 kb · p 0.025 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.214% East Asian · 96/44,864 alleles

Filtering AF 0.179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.166%

Overall 0.00836% 135/1,613,948 alleles · rare exomes 121/1,461,808 · genomes 14/152,140 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.214%	467
South Asian	0.0318%	3,140
Remaining individualsnot grpmax-eligible	0.0128%	7,813
Admixed American	0.00167%	60,006
European (non-Finnish)	8.47e-05%	1,179,948

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.Ser1177Phe
Coding: c.3530C>T
MANE Select: NM_030667
dbSNP: rs200478856
Type: single nucleotide variant
Location: chr12:15589574 (GRCh38)
Gene constraint: LOEUF 0.513 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 77.55 · 2 PDB
Residue 1177: the tyrosine-protein phosphatase 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.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
PTPRO p.Glu564Lys 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-ser1177phe (accessed [today's date]).

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