Is PRKCG p.Pro606= (c.1818T>A) pathogenic?

PRKCG p.Pro606= (c.1818T>A) is classified Likely benign in PRKCG (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-14). Very rare (popmax 0.000957%, nfe); Associated with PRKCG-related disorder.

What condition is associated with PRKCG p.Pro606= (c.1818T>A)?

PRKCG p.Pro606= (c.1818T>A) is associated with PRKCG-related disorder (ClinVar).

How common is PRKCG p.Pro606= (c.1818T>A) in the general population?

PRKCG p.Pro606= (c.1818T>A) is very rare (popmax 0.000957%, nfe) (gnomAD).

PRKCG p.Pro606=

c.1818T>A · rs1225902653 · VCV3034643

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000957%, nfe)

Conditions

PRKCG-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 0.73	GERP -3.9, phastCons 1
Overall
CADD	12.93	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000957% European (non-Finnish) · 11/1,149,148 alleles

Filtering AF 0.000514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000375%

Overall 0.000707% 11/1,555,878 alleles · very rare

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: PRKCG
Protein: p.Pro606=
Coding: c.1818T>A
MANE Select: NM_002739
dbSNP: rs1225902653
Type: single nucleotide variant
Location: chr19:53906370 (GRCh38)
Gene constraint: LOEUF 0.476 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 82.32 · 2 PDB
Residue 606: the protein kinase domain

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

Disease context

PRKCG-related disorder

Similar variants

PRKCG p.Gly63Val Likely pathogenic ★★ same condition
PRKCG p.Ala24Thr Likely pathogenic ★ same condition
PRKCG p.Cys142Ser Likely pathogenic ★ same condition
PRKCG p.His139Tyr Likely pathogenic ★ same condition
PRKCG p.Tyr108Cys Likely pathogenic ★ same condition
PRKCG p.Val138Gly Likely pathogenic ★ same condition
PRKCG p.Arg160Leu Conflicting classifications of pathogenicity ★ ⚠ same condition
PRKCG p.Cys131Tyr Conflicting classifications of pathogenicity ★ ⚠ 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/prkcg-p-pro606 (accessed [today's date]).

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