Is PRKCA p.Gln326= (c.978A>G) pathogenic?

PRKCA p.Gln326= (c.978A>G) is classified Likely benign in PRKCA (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). Very rare (popmax 0.000424%, nfe).

How common is PRKCA p.Gln326= (c.978A>G) in the general population?

PRKCA p.Gln326= (c.978A>G) is very rare (popmax 0.000424%, nfe) (gnomAD).

PRKCA p.Gln326=

c.978A>G · rs538217187 · VCV799737

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

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 -2.1	GERP -3.5
Overall
CADD	0.524	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,032 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,614,084 alleles · very rare exomes 4/1,461,872 · genomes 1/152,212 · joint denominator

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: PRKCA
Protein: p.Gln326=
Coding: c.978A>G
MANE Select: NM_002737
dbSNP: rs538217187
Type: single nucleotide variant
Location: chr17:66732747 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.90 · 6 PDB

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

Similar variants

PRKCA p.Asn279= Benign ★★ same type
PRKCA p.Gly129= Benign ★★ same type
PRKCA p.Leu277= Benign ★★ same type
PRKCA p.Ala356Thr Uncertain significance ★ ⚠ same type
PRKCA p.Arg324Lys Uncertain significance ★ ⚠ same type
PRKCA p.Arg333Gln Uncertain significance ★ ⚠ same type
PRKCA p.Arg496Gly Uncertain significance ★ ⚠ same type
PRKCA p.Asn468Asp Uncertain significance ★ ⚠ same type

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/prkca-p-gln326 (accessed [today's date]).

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