Is PTPRF p.Pro16Leu (c.47C>T) pathogenic?

PTPRF p.Pro16Leu (c.47C>T) is classified Uncertain significance in PTPRF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-28). AlphaMissense: likely benign (0.1462); Rare (popmax 0.102%, sas).

How common is PTPRF p.Pro16Leu (c.47C>T) in the general population?

PTPRF p.Pro16Leu (c.47C>T) is rare (popmax 0.102%, sas) (gnomAD).

What do computational predictors say about PTPRF p.Pro16Leu (c.47C>T)?

AlphaMissense predicts likely benign (score 0.1462) — an in-silico prediction, not a clinical call.

PTPRF p.Pro16Leu

c.47C>T · VCV4147785

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1462 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.102%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1462	likely benign
REVEL	0.171	moderately benign-leaning
SaProt	LLR -2.44	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 2, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 46 kb · p 1.7e-13 · regional, not allelic
Overall
CADD	24.0	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 0.102% South Asian · 89/87,058 alleles

Filtering AF 0.085% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0787%

Overall 0.00635% 101/1,590,824 alleles · rare exomes 92/1,438,528 · genomes 9/152,296 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.102%	978
Remaining individualsnot grpmax-eligible	0.00487%	20,521
African / African-American	0.00403%	24,837
European (non-Finnish)	0.000514%	194,710

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.Pro16Leu
Coding: c.47C>T
MANE Select: NM_002840
Type: single nucleotide variant
Location: chr1:43545122 (GRCh38)
Gene constraint: LOEUF 0.348 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.43 · 13 PDB

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-pro16leu (accessed [today's date]).

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