Is PRKCD p.Val81= (c.243G>C) pathogenic?

PRKCD p.Val81= (c.243G>C) is classified Likely benign in PRKCD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-11). Ultra-rare (popmax 0.0319%, amr); Associated with autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD.

How common is PRKCD p.Val81= (c.243G>C) in the general population?

PRKCD p.Val81= (c.243G>C) is ultra-rare (popmax 0.0319%, amr) (gnomAD).

PRKCD p.Val81=

Q: What condition is associated with PRKCD p.Val81= (c.243G>C)?

PRKCD p.Val81= (c.243G>C) is associated with autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD (ClinVar).

Q: How is EBV-induced lymphoproliferative disease due to PRKCD deficiency inherited?

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

c.243G>C · rs782530190 · VCV726573

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0319%, amr)

Conditions

autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD

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 2.5	GERP -2.6, phastCons 1
Overall
CADD	8.889	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0319% Admixed American · 19/59,518 alleles

Filtering AF 0.0208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0173%

Overall 0.00137% 22/1,608,800 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0319%	3,133
Remaining individualsnot grpmax-eligible	0.00482%	20,755

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: PRKCD
Protein: p.Val81=
Coding: c.243G>C
MANE Select: NM_006254
dbSNP: rs782530190
Type: single nucleotide variant
Location: chr3:53179704 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.29 · 2 PDB
Residue 81: the c2 domain; a β-strand

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

Disease context

autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For EBV-induced lymphoproliferative disease due to PRKCD deficiency (Orphanet):

Inheritance: Autosomal recessive

Similar variants

PRKCD c.787+4C>T Uncertain significance ★★ same condition
PRKCD p.Ala195Val Uncertain significance ★★ ⚠ same condition
PRKCD p.Ala212Val Uncertain significance ★★ ⚠ same condition
PRKCD p.Ala404Gly Uncertain significance ★★ ⚠ same condition
PRKCD p.Arg273Trp Uncertain significance ★★ ⚠ same condition
PRKCD p.Arg40His Uncertain significance ★★ same condition
PRKCD p.Arg444Cys Uncertain significance ★★ same condition
PRKCD p.Arg569His Uncertain significance ★★ ⚠ 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/prkcd-p-val81 (accessed [today's date]).

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