Is PTPRC p.Phe1215= (c.3645C>T) pathogenic?

PTPRC p.Phe1215= (c.3645C>T) is classified Uncertain significance in PTPRC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-09-30). Very rare (popmax 0.00223%, eas); Associated with immunodeficiency 104.

What condition is associated with PTPRC p.Phe1215= (c.3645C>T)?

PTPRC p.Phe1215= (c.3645C>T) is associated with immunodeficiency 104 (ClinVar).

How common is PTPRC p.Phe1215= (c.3645C>T) in the general population?

PTPRC p.Phe1215= (c.3645C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

PTPRC p.Phe1215=

c.3645C>T · rs1558042118 · VCV860752

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

immunodeficiency 104

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.57	GERP -4.5, phastCons 0.063
Overall
CADD	3.428	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,796 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00143% 23/1,613,192 alleles · very rare exomes 23/1,461,210 · genomes 0/151,982 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,796
European (non-Finnish)	0.00178%	56,174
African / African-American	0.00134%	74,850

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.Phe1215=
Coding: c.3645C>T
MANE Select: NM_002838
dbSNP: rs1558042118
Type: single nucleotide variant
Location: chr1:198754404 (GRCh38)
Gene constraint: LOEUF 0.343 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.22 · 6 PDB
Residue 1215: 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 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-phe1215 (accessed [today's date]).

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