Is PRKCD p.Ser89= (c.267G>A) pathogenic?

PRKCD p.Ser89= (c.267G>A) is classified Conflicting classifications of pathogenicity in PRKCD (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-30). Rare (popmax 0.281%, mid); Associated with autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD.

How common is PRKCD p.Ser89= (c.267G>A) in the general population?

PRKCD p.Ser89= (c.267G>A) is rare (popmax 0.281%, mid) (gnomAD).

PRKCD p.Ser89=

Q: What condition is associated with PRKCD p.Ser89= (c.267G>A)?

PRKCD p.Ser89= (c.267G>A) 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.267G>A · rs782214291 · VCV964708

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.281%, mid)

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 -20	GERP -4.9
Overall
CADD	0.217	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.281% Middle Eastern · 17/6,046 alleles

Filtering AF 0.179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.147%

Overall 0.00369% 59/1,598,044 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.281%	356
African / African-American	0.0201%	4,977
Admixed American	0.0172%	5,801
Remaining individualsnot grpmax-eligible	0.00647%	15,457
Ashkenazi Jewishnot grpmax-eligible	0.00341%	29,356
South Asian	0.00112%	89,280
European (non-Finnish)	0.000939%	106,448

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.Ser89=
Coding: c.267G>A
MANE Select: NM_006254
dbSNP: rs782214291
Type: single nucleotide variant
Location: chr3:53179728 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.29 · 2 PDB
Residue 89: the c2 domain; an α-helix

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 p.Ser89Leu Uncertain significance ★ ⚠ same residue
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

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-ser89 (accessed [today's date]).

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