Is PRKDC p.Asp2073= (c.6219C>T) pathogenic?

PRKDC p.Asp2073= (c.6219C>T) is classified Likely benign in PRKDC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-02). Very rare (popmax 0.0022%, sas); Associated with severe combined immunodeficiency due to DNA-PKcs deficiency.

What condition is associated with PRKDC p.Asp2073= (c.6219C>T)?

PRKDC p.Asp2073= (c.6219C>T) is associated with severe combined immunodeficiency due to DNA-PKcs deficiency (ClinVar).

How common is PRKDC p.Asp2073= (c.6219C>T) in the general population?

PRKDC p.Asp2073= (c.6219C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

PRKDC p.Asp2073=

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.6219C>T · rs1411892211 · VCV2560677

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -3.7
Overall
CADD	0.505	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,076 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.00093% 15/1,612,954 alleles · very rare exomes 15/1,460,698 · genomes 0/152,256 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,538
European (non-Finnish)	0.0011%	90,760

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: PRKDC
Protein: p.Asp2073=
Coding: c.6219C>T
MANE Select: NM_006904
dbSNP: rs1411892211
Type: single nucleotide variant
Location: chr8:47858975 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 (gnomAD)
Residue 2073: the 'disordered' region

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.Asp2073His Uncertain significance ★ ⚠ same residue
PRKDC c.2259+6C>T Uncertain significance ★★ same condition
PRKDC c.3464+4G>A Uncertain significance ★★ same condition
PRKDC c.5235+6T>C Uncertain significance ★★ same condition
PRKDC c.5919+5G>A Uncertain significance ★★ same condition
PRKDC p.Ala1008Val Uncertain significance ★★ ⚠ same condition
PRKDC p.Ala1103Val Uncertain significance ★★ ⚠ same condition
PRKDC p.Ala1130Ser 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-asp2073 (accessed [today's date]).

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