Is PRKDC p.Ser3779= (c.11337C>T) pathogenic?

PRKDC p.Ser3779= (c.11337C>T) is classified Benign/Likely benign in PRKDC (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Rare (popmax 0.86%, mid); Associated with severe combined immunodeficiency due to DNA-PKcs deficiency.

What condition is associated with PRKDC p.Ser3779= (c.11337C>T)?

PRKDC p.Ser3779= (c.11337C>T) is associated with severe combined immunodeficiency due to DNA-PKcs deficiency (ClinVar).

How common is PRKDC p.Ser3779= (c.11337C>T) in the general population?

PRKDC p.Ser3779= (c.11337C>T) is rare (popmax 0.86%, mid) (gnomAD).

PRKDC p.Ser3779=

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.11337C>T · rs55789637 · VCV710699

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.86%, mid)

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	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -8	GERP -3.6
Overall
CADD	0.078	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.86% Middle Eastern · 52/6,048 alleles

Filtering AF 0.673% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.607%

Overall 0.0852% 1,362/1,598,134 alleles · rare exomes 1,255/1,445,850 · genomes 107/152,284 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.86%	116
South Asian	0.606%	165
Remaining individualsnot grpmax-eligible	0.0936%	1,068
Admixed American	0.0676%	1,480
European (non-Finnish)	0.0562%	1,780
Ashkenazi Jewishnot grpmax-eligible	0.0239%	4,181
African / African-American	0.0107%	9,349
Finnishnot grpmax-eligible	0.00164%	61,050

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.Ser3779=
Coding: c.11337C>T
MANE Select: NM_006904
dbSNP: rs55789637
Type: single nucleotide variant
Location: chr8:47782437 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 (gnomAD)
Residue 3779: an α-helix; the pi3k/pi4k catalytic domain

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.Ser3779Phe Likely benign ★★ 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-ser3779 (accessed [today's date]).

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