Is PRKCG p.Cys69= (c.207C>T) pathogenic?

PRKCG p.Cys69= (c.207C>T) is classified Benign in PRKCG (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-09-08). Common (popmax 5.86%, afr) — too common for a highly-penetrant pathogenic allele; Associated with spinocerebellar ataxia type 14.

What condition is associated with PRKCG p.Cys69= (c.207C>T)?

PRKCG p.Cys69= (c.207C>T) is associated with spinocerebellar ataxia type 14 (ClinVar).

How is Spinocerebellar ataxia type 14 inherited?

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

PRKCG p.Cys69=

Q: How common is PRKCG p.Cys69= (c.207C>T) in the general population?

PRKCG p.Cys69= (c.207C>T) is common (popmax 5.86%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.207C>T · rs307955 · VCV330057

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 5.86%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

spinocerebellar ataxia type 14

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 5.8	GERP 1.7, phastCons 1
Overall
CADD	13.21	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.86% African / African-American · 4,400/75,028 alleles

Filtering AF 5.72% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.66%

Overall 2.37% 38,267/1,613,944 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.86%	17
Finnishnot grpmax-eligible	3.23%	31
South Asian	2.69%	37
European (non-Finnish)	2.28%	44
Remaining individualsnot grpmax-eligible	2.21%	45
Admixed American	1.16%	86
Ashkenazi Jewishnot grpmax-eligible	1.05%	95
Middle Eastern	1.04%	96
East Asian	0.0111%	8,976

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.Cys69=
Coding: c.207C>T
MANE Select: NM_002739
dbSNP: rs307955
Type: single nucleotide variant
Location: chr19:53884165 (GRCh38)
Gene constraint: LOEUF 0.476 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 82.32 · 2 PDB
Residue 69: a turn

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.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
PRKCG p.Val138Glu 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-cys69 (accessed [today's date]).

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