Is PRKCD p.Asp60= (c.180T>C) pathogenic?

PRKCD p.Asp60= (c.180T>C) is classified Benign/Likely benign in PRKCD (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 17.4%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD.

PRKCD p.Asp60=

Q: What condition is associated with PRKCD p.Asp60= (c.180T>C)?

PRKCD p.Asp60= (c.180T>C) is associated with autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD (ClinVar).

Q: How common is PRKCD p.Asp60= (c.180T>C) in the general population?

PRKCD p.Asp60= (c.180T>C) is common (popmax 17.4%, nfe) — 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.180T>C · rs2230493 · VCV403344

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 17.4%, nfe) — 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 -7.9	GERP -4.9
Overall
CADD	0.266	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 17.4% European (non-Finnish) · 204,943/1,179,858 alleles

Filtering AF 17.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 17.3%

Overall 15.6% 252,154/1,613,930 alleles · common exomes 233,451/1,461,676 · genomes 18,703/152,254 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	18.3%	5
European (non-Finnish)grpmax	17.4%	6
Middle Eastern	16.2%	6
South Asian	16.1%	6
Ashkenazi Jewishnot grpmax-eligible	14.8%	7
Remaining individualsnot grpmax-eligible	14.6%	7
Finnishnot grpmax-eligible	12.3%	8
Admixed American	7.95%	13
African / African-American	6.19%	16
East Asian	1.39%	72

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp60=
Coding: c.180T>C
MANE Select: NM_006254
dbSNP: rs2230493
Type: single nucleotide variant
Location: chr3:53179641 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.29 · 2 PDB
Residue 60: 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-asp60 (accessed [today's date]).

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