Is PRKDC p.Ala2147= (c.6441C>G) pathogenic?

PRKDC p.Ala2147= (c.6441C>G) is classified Benign/Likely benign in PRKDC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-28). Rare (popmax 0.874%, sas); Associated with severe combined immunodeficiency due to DNA-PKcs deficiency.

What condition is associated with PRKDC p.Ala2147= (c.6441C>G)?

PRKDC p.Ala2147= (c.6441C>G) is associated with severe combined immunodeficiency due to DNA-PKcs deficiency (ClinVar).

How common is PRKDC p.Ala2147= (c.6441C>G) in the general population?

PRKDC p.Ala2147= (c.6441C>G) is rare (popmax 0.874%, sas) (gnomAD).

PRKDC p.Ala2147=

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.6441C>G · rs376156239 · VCV475234

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.874%, 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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.9	GERP 0.35, phastCons 1
Overall
CADD	8.329	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.874% South Asian · 707/80,936 alleles

Filtering AF 0.82% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.799%

Overall 0.0491% 750/1,526,380 alleles · rare exomes 699/1,374,128 · genomes 51/152,252 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.874%	114
Remaining individualsnot grpmax-eligible	0.0574%	1,741
Middle Eastern	0.0516%	1,939
African / African-American	0.00276%	36,250
East Asian	0.0023%	43,452
Admixed American	0.00208%	48,160
European (non-Finnish)	0.000178%	563,114

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.Ala2147=
Coding: c.6441C>G
MANE Select: NM_006904
dbSNP: rs376156239
Type: single nucleotide variant
Location: chr8:47858540 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 (gnomAD)
Residue 2147: an α-helix

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.Ala2147Thr Uncertain significance ★ ⚠ same residue
PRKDC p.Ala2147Gly 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

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-ala2147 (accessed [today's date]).

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