Is PRKCD p.Phe557= (c.1671C>T) pathogenic?

PRKCD p.Phe557= (c.1671C>T) is classified Likely benign in PRKCD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-27). Very rare (popmax 0.00891%, eas); Associated with autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD.

What condition is associated with PRKCD p.Phe557= (c.1671C>T)?

PRKCD p.Phe557= (c.1671C>T) is associated with autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD (ClinVar).

How common is PRKCD p.Phe557= (c.1671C>T) in the general population?

PRKCD p.Phe557= (c.1671C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

PRKCD p.Phe557=

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.1671C>T · rs147601598 · VCV720204

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

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 -9.3	GERP -5.3
Overall
CADD	5.884	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,898 alleles

Filtering AF 0.00656% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00608%

Overall 0.00663% 107/1,614,048 alleles · very rare exomes 101/1,461,830 · genomes 6/152,218 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,225
Remaining individualsnot grpmax-eligible	0.008%	12,497
European (non-Finnish)	0.00788%	12,689
African / African-American	0.004%	24,977
South Asian	0.0022%	45,534

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.Phe557=
Coding: c.1671C>T
MANE Select: NM_006254
dbSNP: rs147601598
Type: single nucleotide variant
Location: chr3:53189174 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.29 · 2 PDB
Residue 557: 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-phe557 (accessed [today's date]).

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