Is PTPRC p.Pro1283Arg (c.3848C>G) pathogenic?

PTPRC p.Pro1283Arg (c.3848C>G) is classified Uncertain significance in PTPRC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-20). AlphaMissense: likely benign (0.1052); Very rare (popmax 0.00144%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PTPRC p.Pro1283Arg (c.3848C>G)?

PTPRC p.Pro1283Arg (c.3848C>G) is associated with Inborn genetic diseases, immunodeficiency 104 (ClinVar).

How common is PTPRC p.Pro1283Arg (c.3848C>G) in the general population?

PTPRC p.Pro1283Arg (c.3848C>G) is very rare (popmax 0.00144%, nfe) (gnomAD).

What do computational predictors say about PTPRC p.Pro1283Arg (c.3848C>G)?

AlphaMissense predicts likely benign (score 0.1052) — an in-silico prediction, not a clinical call.

PTPRC p.Pro1283Arg

c.3848C>G · rs775293081 · VCV1010170

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1052 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1052	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -6.62	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 0.35	GERP -0.28
Regional constraint	o/e 1.03	unconstrained · MANE · 7,996 bp · p 0.59 · regional, not allelic
Overall
CADD	15.01	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 0.00144% European (non-Finnish) · 17/1,179,682 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000718%

Overall 0.00105% 17/1,613,292 alleles · very rare exomes 15/1,461,208 · genomes 2/152,084 · joint denominator

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: PTPRC
Protein: p.Pro1283Arg
Coding: c.3848C>G
MANE Select: NM_002838
dbSNP: rs775293081
Type: single nucleotide variant
Location: chr1:198756108 (GRCh38)
Gene constraint: LOEUF 0.343 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.22 · 6 PDB
Residue 1283: the 'disordered' region; a UniProt-annotated variant site (in imd105)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: immunodeficiency 104

Similar variants

PTPRC p.Pro1283= Likely benign ★ same residue
PTPRC c.583+1G>A Likely pathogenic ★★ same condition
PTPRC c.583+1G>T Likely pathogenic ★★ same condition
PTPRC p.Arg890Ter Pathogenic/Likely pathogenic ★★ same condition
PTPRC c.1830-3C>T Uncertain significance ★★ same condition
PTPRC c.3509+5G>A Uncertain significance ★★ same condition
PTPRC p.Ala113Ser Uncertain significance ★★ ⚠ same condition
PTPRC p.Ala1189Val 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/ptprc-p-pro1283arg (accessed [today's date]).

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