Is PTPRC p.Val503Phe (c.1507G>T) pathogenic?

PTPRC p.Val503Phe (c.1507G>T) is classified Uncertain significance in PTPRC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-24). AlphaMissense: likely pathogenic (0.691); Very rare (popmax 8.48e-05%, nfe); Associated with immunodeficiency 104.

What condition is associated with PTPRC p.Val503Phe (c.1507G>T)?

PTPRC p.Val503Phe (c.1507G>T) is associated with immunodeficiency 104 (ClinVar).

How common is PTPRC p.Val503Phe (c.1507G>T) in the general population?

PTPRC p.Val503Phe (c.1507G>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about PTPRC p.Val503Phe (c.1507G>T)?

AlphaMissense predicts likely pathogenic (score 0.691) — an in-silico prediction, not a clinical call.

PTPRC p.Val503Phe

c.1507G>T · rs1193789799 · VCV1951355

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.691 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency 104

Computational evidence

Protein change
AlphaMissense	0.691	likely pathogenic
REVEL	0.282	benign-leaning
SaProt	LLR -11.49	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP -1.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 103 kb · p 0.0009 · regional, not allelic
Overall
CADD	17.44	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 8.48e-05% European (non-Finnish) · 1/1,179,886 alleles

Overall 6.2e-05% 1/1,613,850 alleles · very rare exomes 0/1,461,722 · genomes 1/152,128 · 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.Val503Phe
Coding: c.1507G>T
MANE Select: NM_002838
dbSNP: rs1193789799
Type: single nucleotide variant
Location: chr1:198718150 (GRCh38)
Gene constraint: LOEUF 0.343 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.22 · 6 PDB
Residue 503: the fibronectin type-iii 2 domain; 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.Val503Ile Uncertain significance ★ ⚠ same residue
PTPRC p.Val503= 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

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-val503phe (accessed [today's date]).

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