Is PTPRC p.Ser1139Pro (c.3415T>C) pathogenic?

PTPRC p.Ser1139Pro (c.3415T>C) is classified Uncertain significance in PTPRC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-14). AlphaMissense: likely benign (0.3002); Very rare (popmax 0.00134%, afr); Associated with immunodeficiency 104.

What condition is associated with PTPRC p.Ser1139Pro (c.3415T>C)?

PTPRC p.Ser1139Pro (c.3415T>C) is associated with immunodeficiency 104 (ClinVar).

How common is PTPRC p.Ser1139Pro (c.3415T>C) in the general population?

PTPRC p.Ser1139Pro (c.3415T>C) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about PTPRC p.Ser1139Pro (c.3415T>C)?

AlphaMissense predicts likely benign (score 0.3002) — an in-silico prediction, not a clinical call.

PTPRC p.Ser1139Pro

c.3415T>C · rs937199866 · VCV1042643

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3002 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency 104

Computational evidence

Protein change
AlphaMissense	0.3002	likely benign
REVEL	0.207	benign-leaning
SaProt	LLR -11.76	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.066	GERP -0.46, phastCons 0.001
Regional constraint	o/e 1.03	unconstrained · MANE · 7,996 bp · p 0.59 · regional, not allelic
Overall
CADD	19.16	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 0.00134% African / African-American · 1/74,836 alleles

Overall 6.2e-05% 1/1,612,738 alleles · very rare exomes 0/1,460,728 · genomes 1/152,010 · 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.Ser1139Pro
Coding: c.3415T>C
MANE Select: NM_002838
dbSNP: rs937199866
Type: single nucleotide variant
Location: chr1:198752678 (GRCh38)
Gene constraint: LOEUF 0.343 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.22 · 6 PDB
Residue 1139: an α-helix; a UniProt-annotated variant site (in imd105); the tyrosine-protein phosphatase 2 domain

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.Ser1139Phe Uncertain significance ★ ⚠ 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-ser1139pro (accessed [today's date]).

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