Is PRKCD p.Ala23Val (c.68C>T) pathogenic?

PRKCD p.Ala23Val (c.68C>T) is classified Conflicting classifications of pathogenicity in PRKCD (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-18). AlphaMissense: likely benign (0.0685); Rare (popmax 0.463%, mid); Associated with Inborn genetic diseases.

What condition is associated with PRKCD p.Ala23Val (c.68C>T)?

PRKCD p.Ala23Val (c.68C>T) is associated with Inborn genetic diseases, autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD (ClinVar).

How common is PRKCD p.Ala23Val (c.68C>T) in the general population?

PRKCD p.Ala23Val (c.68C>T) is rare (popmax 0.463%, mid) (gnomAD).

What do computational predictors say about PRKCD p.Ala23Val (c.68C>T)?

AlphaMissense predicts likely benign (score 0.0685) — an in-silico prediction, not a clinical call.

PRKCD p.Ala23Val

c.68C>T · rs144572650 · VCV660963

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0685 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.463%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0685	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -6.69	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 0.81	GERP -4, phastCons 0.003
Regional constraint	o/e 0.71	unconstrained · MANE · 3,131 bp · p 1.2e-05 · regional, not allelic
Overall
CADD	10.32	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

Grpmax group 0.463% Middle Eastern · 26/5,618 alleles

Filtering AF 0.324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.278%

Overall 0.0189% 305/1,613,144 alleles · rare exomes 245/1,460,802 · genomes 60/152,342 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.463%	216
African / African-American	0.06%	1,667
Admixed American	0.0383%	2,609
Remaining individualsnot grpmax-eligible	0.0288%	3,469
European (non-Finnish)	0.0158%	6,343
Finnishnot grpmax-eligible	0.00471%	21,243
South Asian	0.00439%	22,763

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.Ala23Val
Coding: c.68C>T
MANE Select: NM_006254
dbSNP: rs144572650
Type: single nucleotide variant
Location: chr3:53178490 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.29 · 2 PDB
Residue 23: the c2 domain; a β-strand

Full PRKCD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD

Similar variants

PRKCD p.Ala23= Likely 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.Ala454Thr Uncertain significance ★★ same condition
PRKCD p.Arg273Trp Uncertain significance ★★ ⚠ same condition
PRKCD p.Arg40His 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-ala23val (accessed [today's date]).

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