Is PRKDC p.Phe1863fs (c.5589del) pathogenic?

PRKDC p.Phe1863fs (c.5589del) is classified Likely pathogenic in PRKDC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-24). Associated with severe combined immunodeficiency due to DNA-PKcs deficiency.

What condition is associated with PRKDC p.Phe1863fs (c.5589del)?

PRKDC p.Phe1863fs (c.5589del) is associated with severe combined immunodeficiency due to DNA-PKcs deficiency (ClinVar).

PRKDC p.Phe1863fs

Q: How is Severe combined immunodeficiency due to DNA-PKcs deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.5589del · VCV4813774

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

severe combined immunodeficiency due to DNA-PKcs deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 42 of 86
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 1.3, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: PRKDC
Protein: p.Phe1863fs
Coding: c.5589del
MANE Select: NM_006904
Type: Deletion
Location: chr8:47863560 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 (gnomAD)
Residue 1863: an α-helix

Full PRKDC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

severe combined immunodeficiency due to DNA-PKcs deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Severe combined immunodeficiency due to DNA-PKcs deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

PRKDC p.Phe1863= Likely benign ★ same residue
PRKDC p.Glu1050del Uncertain significance ★★ same condition
PRKDC c.4072-12_4072-9del Benign/Likely benign ★★ same condition
PRKDC c.7455-11_7455-10del Likely benign ★★ same condition
PRKDC c.7554-16del Benign/Likely benign ★★ same condition
PRKDC c.9337-5_9337-4del Benign/Likely benign ★★ same condition
PRKDC p.Gly2113del Benign/Likely benign ★★ same condition
PRKDC c.10117-21_10117-16del 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/prkdc-p-phe1863fs (accessed [today's date]).

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