Is PTPRC p.Arg973= (c.2919G>A) pathogenic?

PTPRC p.Arg973= (c.2919G>A) is classified Likely benign in PTPRC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-05). Very rare (popmax 0.00111%, sas); Associated with immunodeficiency 104.

What condition is associated with PTPRC p.Arg973= (c.2919G>A)?

PTPRC p.Arg973= (c.2919G>A) is associated with immunodeficiency 104 (ClinVar).

How common is PTPRC p.Arg973= (c.2919G>A) in the general population?

PTPRC p.Arg973= (c.2919G>A) is very rare (popmax 0.00111%, sas) (gnomAD).

PTPRC p.Arg973=

c.2919G>A · VCV3711994

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00111%, sas)

Conditions

immunodeficiency 104

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.22	donor gain · deltas
Constraint at this position
Conservation	phyloP 2	GERP -0.5, phastCons 1
Overall
CADD	14.57	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00111% South Asian · 1/90,332 alleles

Overall 0.000125% 2/1,605,852 alleles · very rare exomes 1/1,455,164 · genomes 1/150,688 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.11%	912
South Asiangrpmax	0.00111%	90,332

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg973=
Coding: c.2919G>A
MANE Select: NM_002838
Type: single nucleotide variant
Location: chr1:198748180 (GRCh38)
Gene constraint: LOEUF 0.343 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.22 · 6 PDB
Residue 973: 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 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
PTPRC p.Ala60Thr 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-arg973 (accessed [today's date]).

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