Is PRKCD p.Ala102Val (c.305C>T) pathogenic?

PRKCD p.Ala102Val (c.305C>T) is classified Uncertain significance in PRKCD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-27). AlphaMissense: likely benign (0.1521); Absent from gnomAD v4.1; Associated with autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD.

What condition is associated with PRKCD p.Ala102Val (c.305C>T)?

PRKCD p.Ala102Val (c.305C>T) is associated with autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD (ClinVar).

How common is PRKCD p.Ala102Val (c.305C>T) in the general population?

PRKCD p.Ala102Val (c.305C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRKCD p.Ala102Val (c.305C>T)?

AlphaMissense predicts likely benign (score 0.1521) — an in-silico prediction, not a clinical call.

PRKCD p.Ala102Val

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.305C>T · rs2107257453 · VCV1061971

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1521 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD

Computational evidence

Protein change
AlphaMissense	0.1521	likely benign
REVEL	0.223	benign-leaning
SaProt	LLR -12.18	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.82	donor gain, 2 bp away · raw score · deltas
Pangolin	Δ0.30	gain · loss 0.06 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 3,131 bp · p 1.2e-05 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRKCD
Protein: p.Ala102Val
Coding: c.305C>T
MANE Select: NM_006254
dbSNP: rs2107257453
Type: single nucleotide variant
Location: chr3:53179766 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.29 · 2 PDB
Residue 102: 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-ala102val (accessed [today's date]).

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