Is PRKCG p.Pro524Arg (c.1571C>G) pathogenic?

PRKCG p.Pro524Arg (c.1571C>G) is classified Uncertain significance in PRKCG (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). AlphaMissense: likely pathogenic (0.9994); Absent from gnomAD v4.1; Associated with spinocerebellar ataxia type 14.

What condition is associated with PRKCG p.Pro524Arg (c.1571C>G)?

PRKCG p.Pro524Arg (c.1571C>G) is associated with spinocerebellar ataxia type 14 (ClinVar).

How common is PRKCG p.Pro524Arg (c.1571C>G) in the general population?

PRKCG p.Pro524Arg (c.1571C>G) is absent from gnomAD v4.1 (gnomAD).

How is Spinocerebellar ataxia type 14 inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about PRKCG p.Pro524Arg (c.1571C>G)?

AlphaMissense predicts likely pathogenic (score 0.9994) — an in-silico prediction, not a clinical call.

PRKCG p.Pro524Arg

c.1571C>G · rs2068757688 · VCV1705423

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9994 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

spinocerebellar ataxia type 14

Computational evidence

Protein change
AlphaMissense	0.9994	likely pathogenic · top 7% in PRKCG
REVEL	0.905	moderately pathogenic-leaning
SaProt	LLR -16.91	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 6,208 bp · p 5.1e-06 · regional, not allelic
Overall
CADD	30.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRKCG
Protein: p.Pro524Arg
Coding: c.1571C>G
MANE Select: NM_002739
dbSNP: rs2068757688
Type: single nucleotide variant
Location: chr19:53900745 (GRCh38)
Gene constraint: LOEUF 0.476 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 82.32 · 2 PDB
Residue 524: the protein kinase domain

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

Disease context

spinocerebellar ataxia type 14 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Spinocerebellar ataxia type 14 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood, Elderly

Similar variants

PRKCG p.Pro524= Likely benign ★ same residue
PRKCG p.Gln127Arg Pathogenic ★★ same condition
PRKCG p.Gln127Lys Likely pathogenic ★★ same condition
PRKCG p.Gly63Val Likely pathogenic ★★ same condition
PRKCG p.His101Tyr Pathogenic/Likely pathogenic ★★ same condition
PRKCG p.His74Asn Likely pathogenic ★★ same condition
PRKCG p.His74Tyr Likely pathogenic ★★ same condition
PRKCG p.Leu120Phe Likely pathogenic ★★ 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-pro524arg (accessed [today's date]).

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