Is PRKCD p.Val72Met (c.214G>A) pathogenic?

PRKCD p.Val72Met (c.214G>A) is classified Uncertain significance in PRKCD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-15). AlphaMissense: likely benign (0.1242); Ultra-rare (popmax 0.0111%, eas); Associated with autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD.

What condition is associated with PRKCD p.Val72Met (c.214G>A)?

PRKCD p.Val72Met (c.214G>A) is associated with autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD (ClinVar).

How common is PRKCD p.Val72Met (c.214G>A) in the general population?

PRKCD p.Val72Met (c.214G>A) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about PRKCD p.Val72Met (c.214G>A)?

AlphaMissense predicts likely benign (score 0.1242) — an in-silico prediction, not a clinical call.

PRKCD p.Val72Met

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.214G>A · rs151061939 · VCV837398

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1242 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD

Computational evidence

Protein change
AlphaMissense	0.1242	likely benign
REVEL	0.25	benign-leaning
SaProt	LLR -8.19	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.3, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 3,131 bp · p 1.2e-05 · regional, not allelic
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,876 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.000342% 5/1,460,762 alleles · ultra-rare

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.Val72Met
Coding: c.214G>A
MANE Select: NM_006254
dbSNP: rs151061939
Type: single nucleotide variant
Location: chr3:53179675 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.29 · 2 PDB
Residue 72: 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 p.Val72Leu Benign ★★ same residue
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

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-val72met (accessed [today's date]).

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