Is PTPRF p.Arg487Cys (c.1459C>T) pathogenic?

PTPRF p.Arg487Cys (c.1459C>T) is classified Uncertain significance in PTPRF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-02). AlphaMissense: ambiguous (0.4564); Ultra-rare (popmax 0.0165%, mid).

How common is PTPRF p.Arg487Cys (c.1459C>T) in the general population?

PTPRF p.Arg487Cys (c.1459C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about PTPRF p.Arg487Cys (c.1459C>T)?

AlphaMissense predicts ambiguous (score 0.4564) — an in-silico prediction, not a clinical call.

PTPRF p.Arg487Cys

c.1459C>T · VCV4147794

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4564 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Computational evidence

Protein change
AlphaMissense	0.4564	ambiguous
REVEL	0.615	indeterminate
SaProt	LLR -10.11	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP -0.042, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 6,728 bp · p 0.011 · regional, not allelic
Overall
CADD	32.0	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 0.0165% Middle Eastern · 1/6,064 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.002% 32/1,598,172 alleles · ultra-rare exomes 30/1,445,916 · genomes 2/152,256 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,064
Remaining individualsnot grpmax-eligible	0.00807%	12,398
European (non-Finnish)	0.00204%	48,954
Admixed American	0.00169%	59,106
African / African-American	0.00134%	74,814

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.Arg487Cys
Coding: c.1459C>T
MANE Select: NM_002840
Type: single nucleotide variant
Location: chr1:43591481 (GRCh38)
Gene constraint: LOEUF 0.348 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.43 · 13 PDB
Residue 487: a β-strand; the fibronectin type-iii 2 domain

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

Similar variants

PTPRF p.Gly1143Ser Uncertain significance ★★ ⚠ same type
PTPRF p.His1730Gln Uncertain significance ★★ ⚠ same type
PTPRF c.1531+9G>A Benign/Likely benign ★★ same type
PTPRF c.1668+10G>C Benign/Likely benign ★★ same type
PTPRF c.237+5G>A Benign ★★ same type
PTPRF c.3974-9C>T Benign ★★ same type
PTPRF p.Ala1659= Benign ★★ same type
PTPRF p.Ala356Ser Likely benign ★★ same type

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-arg487cys (accessed [today's date]).

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