Is PRKDC p.Pro3677Ser (c.11029C>T) pathogenic?

PRKDC p.Pro3677Ser (c.11029C>T) is classified Uncertain significance in PRKDC (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-09-11). AlphaMissense: ambiguous (0.3418); Ultra-rare (popmax 0.0823%, nfe); Associated with severe combined immunodeficiency due to DNA-PKcs deficiency.

What condition is associated with PRKDC p.Pro3677Ser (c.11029C>T)?

PRKDC p.Pro3677Ser (c.11029C>T) is associated with severe combined immunodeficiency due to DNA-PKcs deficiency (ClinVar).

How common is PRKDC p.Pro3677Ser (c.11029C>T) in the general population?

PRKDC p.Pro3677Ser (c.11029C>T) is ultra-rare (popmax 0.0823%, nfe) (gnomAD).

What do computational predictors say about PRKDC p.Pro3677Ser (c.11029C>T)?

AlphaMissense predicts ambiguous (score 0.3418) — an in-silico prediction, not a clinical call.

PRKDC p.Pro3677Ser

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.11029C>T · rs55924155 · VCV444752

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.3418 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0823%, nfe)

Conditions

severe combined immunodeficiency due to DNA-PKcs deficiency

Computational evidence

Protein change
AlphaMissense	0.3418	ambiguous
REVEL	0.417	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 25 kb · p 7.5e-15 · regional, not allelic
Overall
CADD	20.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0823% European (non-Finnish) · 971/1,179,868 alleles

Filtering AF 0.0779% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0763%

Overall 0.0642% 1,036/1,613,868 alleles · ultra-rare exomes 962/1,461,684 · genomes 74/152,184 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0823%	1,215
Admixed American	0.0433%	2,308
Remaining individualsnot grpmax-eligible	0.0352%	2,840
African / African-American	0.0213%	4,687
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604

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.Pro3677Ser
Coding: c.11029C>T
MANE Select: NM_006904
dbSNP: rs55924155
Type: single nucleotide variant
Location: chr8:47785191 (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.Pro3677Thr 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-pro3677ser (accessed [today's date]).

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