Is PRKDC p.Ser606= (c.1818A>G) pathogenic?

PRKDC p.Ser606= (c.1818A>G) is classified Likely benign in PRKDC (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-27). Ultra-rare (popmax 0.0651%, nfe); Associated with severe combined immunodeficiency due to DNA-PKcs deficiency.

What condition is associated with PRKDC p.Ser606= (c.1818A>G)?

PRKDC p.Ser606= (c.1818A>G) is associated with severe combined immunodeficiency due to DNA-PKcs deficiency (ClinVar).

How common is PRKDC p.Ser606= (c.1818A>G) in the general population?

PRKDC p.Ser606= (c.1818A>G) is ultra-rare (popmax 0.0651%, nfe) (gnomAD).

PRKDC p.Ser606=

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.1818A>G · rs368804788 · VCV542020

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0651%, nfe)

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 1.2	GERP 1.8, phastCons 1
Overall
CADD	9.055	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0651% European (non-Finnish) · 761/1,168,282 alleles

Filtering AF 0.0613% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0597%

Overall 0.0517% 822/1,590,880 alleles · ultra-rare exomes 767/1,438,544 · genomes 55/152,336 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0651%	1,535
Remaining individualsnot grpmax-eligible	0.0535%	1,870
Finnishnot grpmax-eligible	0.0255%	3,920
Admixed American	0.0106%	9,461
African / African-American	0.00671%	14,896
South Asian	0.00115%	86,750

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.Ser606=
Coding: c.1818A>G
MANE Select: NM_006904
dbSNP: rs368804788
Type: single nucleotide variant
Location: chr8:47930746 (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.Ser606Ala 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-ser606 (accessed [today's date]).

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