Is PRKCB p.Pro669= (c.2007C>T) pathogenic?

PRKCB p.Pro669= (c.2007C>T) is classified Likely benign in PRKCB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-10). Ultra-rare (popmax 0.0384%, sas); Associated with PRKCB-related disorder.

What condition is associated with PRKCB p.Pro669= (c.2007C>T)?

PRKCB p.Pro669= (c.2007C>T) is associated with PRKCB-related disorder (ClinVar).

How common is PRKCB p.Pro669= (c.2007C>T) in the general population?

PRKCB p.Pro669= (c.2007C>T) is ultra-rare (popmax 0.0384%, sas) (gnomAD).

PRKCB p.Pro669=

c.2007C>T · rs772098050 · VCV3041976

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0384%, sas)

Conditions

PRKCB-related disorder

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 0.41	GERP -4.1, phastCons 1
Overall
CADD	9.324	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0384% South Asian · 35/91,056 alleles

Filtering AF 0.0283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0249%

Overall 0.00366% 59/1,613,942 alleles · ultra-rare exomes 55/1,461,832 · genomes 4/152,110 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0384%	2,602
East Asian	0.0134%	7,482
Remaining individualsnot grpmax-eligible	0.0032%	31,241
Admixed American	0.00167%	59,992
Finnishnot grpmax-eligible	0.00156%	64,032
European (non-Finnish)	0.00119%	84,285

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: PRKCB
Protein: p.Pro669=
Coding: c.2007C>T
MANE Select: NM_002738
dbSNP: rs772098050
Type: single nucleotide variant
Location: chr16:24214801 (GRCh38)
Gene constraint: LOEUF 0.241 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.95 · 8 PDB
Residue 669: the agc-kinase c-terminal domain

Full PRKCB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PRKCB-related disorder

Similar variants

PRKCB p.Gly332Ala Conflicting classifications of pathogenicity ★ ⚠ same condition
PRKCB c.*5171C>T Likely benign same condition
PRKCB p.Arg238= Benign same condition
PRKCB p.Asn298Ser Likely benign same condition
PRKCB p.Lys327= Likely benign same condition
PRKCB p.Pro202= Benign same condition
PRKCB c.1332-10_1332-9del Benign same condition
PRKCB c.1395-4A>G Benign ★★ same type

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/prkcb-p-pro669 (accessed [today's date]).

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