Is PRKCG p.Pro635= (c.1905G>T) pathogenic?

PRKCG p.Pro635= (c.1905G>T) is classified Uncertain significance in PRKCG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-27). Absent from gnomAD v4.1; Associated with spinocerebellar ataxia type 14.

What condition is associated with PRKCG p.Pro635= (c.1905G>T)?

PRKCG p.Pro635= (c.1905G>T) is associated with spinocerebellar ataxia type 14 (ClinVar).

How common is PRKCG p.Pro635= (c.1905G>T) in the general population?

PRKCG p.Pro635= (c.1905G>T) 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.

PRKCG p.Pro635=

c.1905G>T · VCV3896962

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,574,520)

Conditions

spinocerebellar ataxia type 14

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.63	donor loss · deltas
Pangolin	Δ0.75	loss · gain 0.15 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.6	GERP 1.5, phastCons 1
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,574,520). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PRKCG
Protein: p.Pro635=
Coding: c.1905G>T
MANE Select: NM_002739
Type: single nucleotide variant
Location: chr19:53906457 (GRCh38)
Gene constraint: LOEUF 0.476 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 82.32 · 2 PDB
Residue 635: 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.Pro635Leu Uncertain significance ★ ⚠ 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-pro635 (accessed [today's date]).

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