Is PRKCG p.Phe647= (c.1941C>T) pathogenic?

PRKCG p.Phe647= (c.1941C>T) is classified Benign in PRKCG (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-06-24). Common (popmax 7.31%, eas) — too common for a highly-penetrant pathogenic allele; Associated with spinocerebellar ataxia type 14.

What condition is associated with PRKCG p.Phe647= (c.1941C>T)?

PRKCG p.Phe647= (c.1941C>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.Phe647=

Q: How common is PRKCG p.Phe647= (c.1941C>T) in the general population?

PRKCG p.Phe647= (c.1941C>T) is common (popmax 7.31%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1941C>T · rs2242243 · VCV330069

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 7.31%, eas) — 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 5.7	GERP 1.9, phastCons 1
Overall
CADD	15.74	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.31% East Asian · 3,279/44,846 alleles

Filtering AF 7.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.02%

Overall 0.224% 3,617/1,613,346 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	7.31%	14
Remaining individualsnot grpmax-eligible	0.314%	319
South Asian	0.11%	911
Admixed American	0.0267%	3,752
African / African-American	0.004%	25,009
European (non-Finnish)	0.00195%	51,305

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.Phe647=
Coding: c.1941C>T
MANE Select: NM_002739
dbSNP: rs2242243
Type: single nucleotide variant
Location: chr19:53906742 (GRCh38)
Gene constraint: LOEUF 0.476 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 82.32 · 2 PDB
Residue 647: the agc-kinase c-terminal 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.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-phe647 (accessed [today's date]).

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