Is PRKCB p.Pro202= (c.606C>T) pathogenic?

PRKCB p.Pro202= (c.606C>T) is classified Benign in PRKCB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-04). Common (popmax 9.04%, eas) — too common for a highly-penetrant pathogenic allele; Associated with PRKCB-related disorder.

What condition is associated with PRKCB p.Pro202= (c.606C>T)?

PRKCB p.Pro202= (c.606C>T) is associated with PRKCB-related disorder (ClinVar).

PRKCB p.Pro202=

Q: How common is PRKCB p.Pro202= (c.606C>T) in the general population?

PRKCB p.Pro202= (c.606C>T) is common (popmax 9.04%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.606C>T · rs3729896 · VCV3055721

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 9.04%, eas) — too common for a highly-penetrant pathogenic allele

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 -0.066	GERP -3.5, phastCons 0.89
Overall
CADD	11.35	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.04% East Asian · 4,056/44,860 alleles

Filtering AF 8.81% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.71%

Overall 4.01% 64,717/1,614,006 alleles · common exomes 59,174/1,461,778 · genomes 5,543/152,228 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	9.21%	11
East Asiangrpmax	9.04%	11
South Asian	5.25%	19
Finnishnot grpmax-eligible	4.51%	22
Remaining individualsnot grpmax-eligible	4.19%	24
European (non-Finnish)	3.92%	26
Ashkenazi Jewishnot grpmax-eligible	2.92%	34
African / African-American	2.64%	38
Middle Eastern	2.41%	42
Admixed American	1.73%	58

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro202=
Coding: c.606C>T
MANE Select: NM_002738
dbSNP: rs3729896
Type: single nucleotide variant
Location: chr16:24092867 (GRCh38)
Gene constraint: LOEUF 0.241 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.95 · 8 PDB
Residue 202: the c2 domain; a β-strand

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.Pro669= Likely 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-pro202 (accessed [today's date]).

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