Is PRKDC p.Ser3489= (c.10467C>T) pathogenic?

PRKDC p.Ser3489= (c.10467C>T) is classified Likely benign in PRKDC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-06). Ultra-rare (popmax 0.0184%, amr); Associated with severe combined immunodeficiency due to DNA-PKcs deficiency.

What condition is associated with PRKDC p.Ser3489= (c.10467C>T)?

PRKDC p.Ser3489= (c.10467C>T) is associated with severe combined immunodeficiency due to DNA-PKcs deficiency (ClinVar).

How common is PRKDC p.Ser3489= (c.10467C>T) in the general population?

PRKDC p.Ser3489= (c.10467C>T) is ultra-rare (popmax 0.0184%, amr) (gnomAD).

PRKDC p.Ser3489=

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.10467C>T · rs760537334 · VCV1560086

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0184%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -3.1, phastCons 1
Overall
CADD	3.462	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0184% Admixed American · 11/59,844 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00797%

Overall 0.00255% 41/1,607,252 alleles · ultra-rare exomes 35/1,455,026 · genomes 6/152,226 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0184%	5,440
Middle Eastern	0.0165%	6,058
African / African-American	0.00803%	12,460
Remaining individualsnot grpmax-eligible	0.00643%	15,554
South Asian	0.0033%	30,278
European (non-Finnish)	0.00136%	73,393

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.Ser3489=
Coding: c.10467C>T
MANE Select: NM_006904
dbSNP: rs760537334
Type: single nucleotide variant
Location: chr8:47794493 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 (gnomAD)
Residue 3489: the fat 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.Ser3489Cys Uncertain significance ★ ⚠ same residue
PRKDC p.Ser3489Phe Uncertain significance ★ ⚠ same residue
PRKDC p.Ser3489Tyr 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

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-ser3489 (accessed [today's date]).

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