Is PRKCD p.Leu481= (c.1441C>T) pathogenic?

PRKCD p.Leu481= (c.1441C>T) is classified Benign/Likely benign in PRKCD (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Common (popmax 82.5%, eas) — too common for a highly-penetrant pathogenic allele; Associated with autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD.

What condition is associated with PRKCD p.Leu481= (c.1441C>T)?

PRKCD p.Leu481= (c.1441C>T) is associated with autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD (ClinVar).

PRKCD p.Leu481=

Q: How common is PRKCD p.Leu481= (c.1441C>T) in the general population?

PRKCD p.Leu481= (c.1441C>T) is common (popmax 82.5%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.1441C>T · rs2306574 · VCV403346

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 82.5%, eas) — too common for a highly-penetrant pathogenic allele

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 2.8	GERP 2.6, phastCons 1
Overall
CADD	13.46	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 82.5% East Asian · 37,019/44,868 alleles

Filtering AF 81.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 81.5%

Overall 77.2% 1,246,719/1,613,980 alleles · common exomes 1,132,236/1,461,840 · genomes 114,483/152,140 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	82.5%	1
Amishnot grpmax-eligible	79.6%	1
European (non-Finnish)	78.5%	1
Remaining individualsnot grpmax-eligible	76.8%	1
Ashkenazi Jewishnot grpmax-eligible	76.7%	1
Admixed American	75.4%	1
Finnishnot grpmax-eligible	74.3%	1
African / African-American	72.1%	1
Middle Eastern	70%	1
South Asian	66.5%	2

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.Leu481=
Coding: c.1441C>T
MANE Select: NM_006254
dbSNP: rs2306574
Type: single nucleotide variant
Location: chr3:53188745 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.29 · 2 PDB
Residue 481: the protein kinase domain

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-leu481 (accessed [today's date]).

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