Is PRKCD p.Ser304= (c.912A>G) pathogenic?

PRKCD p.Ser304= (c.912A>G) is classified Benign in PRKCD (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-26). Low-frequency (popmax 1.24%, sas); Associated with autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD.

How common is PRKCD p.Ser304= (c.912A>G) in the general population?

PRKCD p.Ser304= (c.912A>G) is low-frequency (popmax 1.24%, sas) (gnomAD).

PRKCD p.Ser304=

Q: What condition is associated with PRKCD p.Ser304= (c.912A>G)?

PRKCD p.Ser304= (c.912A>G) 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.912A>G · rs529176751 · VCV725398

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.24%, sas)

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 -6.2	GERP -3.8
Overall
CADD	0.055	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.24% South Asian · 1,134/91,084 alleles

Filtering AF 1.18% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.16%

Overall 0.0734% 1,185/1,613,486 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.24%	80
Remaining individualsnot grpmax-eligible	0.0768%	1,302
Middle Eastern	0.0165%	6,062
European (non-Finnish)	0.000169%	590,012

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.Ser304=
Coding: c.912A>G
MANE Select: NM_006254
dbSNP: rs529176751
Type: single nucleotide variant
Location: chr3:53185627 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.29 · 2 PDB
Residue 304: a modified residue (phosphoserine; by autocatalysis)

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-ser304 (accessed [today's date]).

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