Is PRKDC p.Asp3706= (c.11118C>T) pathogenic?

PRKDC p.Asp3706= (c.11118C>T) is classified Likely benign in PRKDC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-06-01). Ultra-rare (popmax 0.0533%, amr); Associated with severe combined immunodeficiency due to DNA-PKcs deficiency.

What condition is associated with PRKDC p.Asp3706= (c.11118C>T)?

PRKDC p.Asp3706= (c.11118C>T) is associated with severe combined immunodeficiency due to DNA-PKcs deficiency (ClinVar).

How common is PRKDC p.Asp3706= (c.11118C>T) in the general population?

PRKDC p.Asp3706= (c.11118C>T) is ultra-rare (popmax 0.0533%, amr) (gnomAD).

PRKDC p.Asp3706=

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.11118C>T · rs55660253 · VCV712333

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0533%, amr)

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	<0.2	all four deltas below 0.2 · G>C here scores Δ0.43 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.7	GERP -3.9
Overall
CADD	0.897	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0533% Admixed American · 32/60,010 alleles

Filtering AF 0.0387% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.035%

Overall 0.0325% 525/1,613,838 alleles · ultra-rare exomes 475/1,461,688 · genomes 50/152,150 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0533%	1,875
European (non-Finnish)	0.0392%	2,554
Remaining individualsnot grpmax-eligible	0.024%	4,165
Finnishnot grpmax-eligible	0.0109%	9,141
African / African-American	0.008%	12,495
East Asian	0.00446%	22,438
South Asian	0.0011%	91,074

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.Asp3706=
Coding: c.11118C>T
MANE Select: NM_006904
dbSNP: rs55660253
Type: single nucleotide variant
Location: chr8:47783799 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 (gnomAD)

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.Asp3706His 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-asp3706 (accessed [today's date]).

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