Is PTPRF p.Pro459= (c.1377G>A) pathogenic?

PTPRF p.Pro459= (c.1377G>A) is classified Likely benign in PTPRF (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-04). Rare (popmax 0.229%, afr); Associated with PTPRF-related disorder.

What condition is associated with PTPRF p.Pro459= (c.1377G>A)?

PTPRF p.Pro459= (c.1377G>A) is associated with PTPRF-related disorder (ClinVar).

How common is PTPRF p.Pro459= (c.1377G>A) in the general population?

PTPRF p.Pro459= (c.1377G>A) is rare (popmax 0.229%, afr) (gnomAD).

PTPRF p.Pro459=

c.1377G>A · rs377187180 · VCV3044522

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.229%, afr)

Conditions

PTPRF-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.187	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP -0.67, phastCons 1
Overall
CADD	11.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.229% African / African-American · 169/73,942 alleles

Filtering AF 0.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.19%

Overall 0.0142% 222/1,566,418 alleles · rare exomes 128/1,414,056 · genomes 94/152,362 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.229%	438
Remaining individualsnot grpmax-eligible	0.028%	3,576
Admixed American	0.0206%	4,864
South Asian	0.0128%	7,796
Finnishnot grpmax-eligible	0.00521%	19,179
Ashkenazi Jewishnot grpmax-eligible	0.00347%	28,818
European (non-Finnish)	0.000864%	115,711

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: PTPRF
Protein: p.Pro459=
Coding: c.1377G>A
MANE Select: NM_002840
dbSNP: rs377187180
Type: single nucleotide variant
Location: chr1:43591399 (GRCh38)
Gene constraint: LOEUF 0.348 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.43 · 13 PDB
Residue 459: an α-helix; the fibronectin type-iii 2 domain

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

Disease context

PTPRF-related disorder

Similar variants

PTPRF p.Pro459Leu Likely benign ★ same residue
PTPRF c.3389+4T>G Likely benign same condition
PTPRF c.3974-829C>T Likely benign same condition
PTPRF c.4372-7C>T Likely benign same condition
PTPRF p.Ala157= Benign same condition
PTPRF p.Arg1286= Likely benign same condition
PTPRF p.Asn441= Likely benign same condition
PTPRF p.Asp562Asn 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/ptprf-p-pro459 (accessed [today's date]).

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