Is PTPRC p.Pro1297Ser (c.3889C>T) pathogenic?

PTPRC p.Pro1297Ser (c.3889C>T) is classified Uncertain significance in PTPRC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-02). AlphaMissense: likely benign (0.2581); Absent from gnomAD v4.1; Associated with immunodeficiency 104.

What condition is associated with PTPRC p.Pro1297Ser (c.3889C>T)?

PTPRC p.Pro1297Ser (c.3889C>T) is associated with immunodeficiency 104 (ClinVar).

How common is PTPRC p.Pro1297Ser (c.3889C>T) in the general population?

PTPRC p.Pro1297Ser (c.3889C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PTPRC p.Pro1297Ser (c.3889C>T)?

AlphaMissense predicts likely benign (score 0.2581) — an in-silico prediction, not a clinical call.

PTPRC p.Pro1297Ser

c.3889C>T · rs2102560805 · VCV1490312

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2581 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency 104

Computational evidence

Protein change
AlphaMissense	0.2581	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -5.30	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 2.7	GERP 0.86, phastCons 0.99
Regional constraint	o/e 1.03	unconstrained · MANE · 7,996 bp · p 0.59 · regional, not allelic
Overall
CADD	19.04	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PTPRC
Protein: p.Pro1297Ser
Coding: c.3889C>T
MANE Select: NM_002838
dbSNP: rs2102560805
Type: single nucleotide variant
Location: chr1:198756149 (GRCh38)
Gene constraint: LOEUF 0.343 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.22 · 6 PDB
Residue 1297: 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

immunodeficiency 104 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PTPRC p.Pro1297= 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.Ala191Val 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-pro1297ser (accessed [today's date]).

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