Is PTPRT p.Ser528= (c.1584G>A) pathogenic?

PTPRT p.Ser528= (c.1584G>A) is classified Likely benign in PTPRT (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-30). Rare (popmax 0.347%, amr); Associated with PTPRT-related disorder.

What condition is associated with PTPRT p.Ser528= (c.1584G>A)?

PTPRT p.Ser528= (c.1584G>A) is associated with PTPRT-related disorder (ClinVar).

How common is PTPRT p.Ser528= (c.1584G>A) in the general population?

PTPRT p.Ser528= (c.1584G>A) is rare (popmax 0.347%, amr) (gnomAD).

PTPRT p.Ser528=

c.1584G>A · rs201153898 · VCV3053559

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.347%, amr)

Conditions

PTPRT-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 -8.8	GERP -5.4
Overall
CADD	0.296	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.347% Admixed American · 208/60,002 alleles

Filtering AF 0.308% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.293%

Overall 0.194% 3,130/1,614,042 alleles · rare exomes 2,877/1,461,866 · genomes 253/152,176 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.347%	288
Remaining individualsnot grpmax-eligible	0.24%	417
European (non-Finnish)	0.225%	445
Middle Eastern	0.116%	865
South Asian	0.0845%	1,183
African / African-American	0.0427%	2,344
Ashkenazi Jewishnot grpmax-eligible	0.00675%	14,804
Finnishnot grpmax-eligible	0.00469%	21,341
East Asian	0.00223%	44,866

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: PTPRT
Protein: p.Ser528=
Coding: c.1584G>A
MANE Select: NM_007050
dbSNP: rs201153898
Type: single nucleotide variant
Location: chr20:42352262 (GRCh38)
Gene constraint: LOEUF 0.395 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.99 · 1 PDB
Residue 528: the fibronectin type-iii 3 domain

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

Disease context

PTPRT-related disorder

Similar variants

PTPRT p.Arg1358Pro Uncertain significance ★ ⚠ same condition
PTPRT p.Gly232Ser Uncertain significance ★ ⚠ same condition
PTPRT p.Gly274Val Uncertain significance ★ ⚠ same condition
PTPRT p.Val735Met Uncertain significance ★ ⚠ same condition
PTPRT p.Gln1366Leu Uncertain significance ⚠ same condition
PTPRT c.1154-10T>C Benign same condition
PTPRT c.2683-9G>T Benign same condition
PTPRT c.3099+10T>C 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/ptprt-p-ser528 (accessed [today's date]).

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