Is PRKCA p.Arg324Lys (c.971G>A) pathogenic?

PRKCA p.Arg324Lys (c.971G>A) is classified Uncertain significance in PRKCA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-25). AlphaMissense: likely benign (0.0652); Very rare (popmax 0.0011%, sas).

How common is PRKCA p.Arg324Lys (c.971G>A) in the general population?

PRKCA p.Arg324Lys (c.971G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about PRKCA p.Arg324Lys (c.971G>A)?

AlphaMissense predicts likely benign (score 0.0652) — an in-silico prediction, not a clinical call.

PRKCA p.Arg324Lys

c.971G>A · VCV3783326

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0652 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0652	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -5.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.97, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 246 kb · p 1e-18 · regional, not allelic
Overall
CADD	20.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0011% South Asian · 1/91,072 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000342% 5/1,461,860 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,072
European (non-Finnish)	0.000339%	295,008

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.Arg324Lys
Coding: c.971G>A
MANE Select: NM_002737
Type: single nucleotide variant
Location: chr17:66732740 (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.Arg333Gln Uncertain significance ★ ⚠ same type
PRKCA p.Arg496Gly Uncertain significance ★ ⚠ same type
PRKCA p.Asn468Asp Uncertain significance ★ ⚠ same type
PRKCA p.Asn554Ser 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-arg324lys (accessed [today's date]).

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