Is PRKCA p.Glu593= (c.1779G>A) pathogenic?

PRKCA p.Glu593= (c.1779G>A) is classified Benign in PRKCA (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-20). Common (popmax 31.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with PRKCA-related disorder.

What condition is associated with PRKCA p.Glu593= (c.1779G>A)?

PRKCA p.Glu593= (c.1779G>A) is associated with PRKCA-related disorder (ClinVar).

PRKCA p.Glu593=

Q: How common is PRKCA p.Glu593= (c.1779G>A) in the general population?

PRKCA p.Glu593= (c.1779G>A) is common (popmax 31.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1779G>A · rs2228945 · VCV3060914

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 31.5%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

PRKCA-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 -0.97	GERP -4.3
Overall
CADD	0.842	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 31.5% African / African-American · 23,570/74,938 alleles

Filtering AF 31.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 31%

Overall 9.23% 148,925/1,613,842 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	31.5%	3
East Asian	17.9%	6
Admixed American	10.7%	9
Remaining individualsnot grpmax-eligible	9.97%	10
Ashkenazi Jewishnot grpmax-eligible	9.1%	11
European (non-Finnish)	7.89%	13
Middle Eastern	7.54%	13
South Asian	6.02%	17
Amishnot grpmax-eligible	5.93%	17
Finnishnot grpmax-eligible	4.56%	22

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: PRKCA
Protein: p.Glu593=
Coding: c.1779G>A
MANE Select: NM_002737
dbSNP: rs2228945
Type: single nucleotide variant
Location: chr17:66788904 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.90 · 6 PDB
Residue 593: the protein kinase domain

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

Disease context

PRKCA-related disorder

Similar variants

PRKCA p.Asp96Glu Uncertain significance ⚠ same condition
PRKCA p.Pro93= Likely benign same condition
PRKCA p.Gly257fs Uncertain significance same condition
PRKCA c.-4dup Likely benign same condition
PRKCA p.Asn279= Benign ★★ same type
PRKCA p.Gly129= Benign ★★ same type
PRKCA p.Leu277= Benign ★★ same type
PRKCA p.Ala356Thr Uncertain significance ★ ⚠ 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/prkca-p-glu593 (accessed [today's date]).

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