Is PTPRC p.Pro291Ser (c.871C>T) pathogenic?

PTPRC p.Pro291Ser (c.871C>T) is classified Uncertain significance in PTPRC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-12). AlphaMissense: likely benign (0.1682); Very rare (popmax 0.0051%, nfe); Associated with immunodeficiency 104.

What condition is associated with PTPRC p.Pro291Ser (c.871C>T)?

PTPRC p.Pro291Ser (c.871C>T) is associated with immunodeficiency 104 (ClinVar).

How common is PTPRC p.Pro291Ser (c.871C>T) in the general population?

PTPRC p.Pro291Ser (c.871C>T) is very rare (popmax 0.0051%, nfe) (gnomAD).

What do computational predictors say about PTPRC p.Pro291Ser (c.871C>T)?

AlphaMissense predicts likely benign (score 0.1682) — an in-silico prediction, not a clinical call.

PTPRC p.Pro291Ser

c.871C>T · rs762697900 · VCV2152874

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1682 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0051%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency 104

Computational evidence

Protein change
AlphaMissense	0.1682	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -9.45	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 -2.1	GERP -0.8
Regional constraint	o/e 0.89	unconstrained · MANE · 103 kb · p 0.0009 · regional, not allelic
Overall
CADD	4.724	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 0.0051% European (non-Finnish) · 60/1,177,198 alleles

Filtering AF 0.00403% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00363%

Overall 0.00397% 64/1,610,716 alleles · very rare exomes 61/1,458,544 · genomes 3/152,172 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0051%	19,620
Remaining individualsnot grpmax-eligible	0.00321%	31,181
Admixed American	0.00167%	60,004
African / African-American	0.00134%	74,846

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.Pro291Ser
Coding: c.871C>T
MANE Select: NM_002838
dbSNP: rs762697900
Type: single nucleotide variant
Location: chr1:198706919 (GRCh38)
Gene constraint: LOEUF 0.343 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.22 · 6 PDB
Residue 291: a β-strand

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.Pro291= 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-pro291ser (accessed [today's date]).

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