Is PRKCD p.Arg273Trp (c.817C>T) pathogenic?

PRKCD p.Arg273Trp (c.817C>T) is classified Uncertain significance in PRKCD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-22). AlphaMissense: likely benign (0.1882); Very rare (popmax 0.00329%, sas); Associated with Inborn genetic diseases.

What condition is associated with PRKCD p.Arg273Trp (c.817C>T)?

PRKCD p.Arg273Trp (c.817C>T) is associated with Inborn genetic diseases, autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD (ClinVar).

How common is PRKCD p.Arg273Trp (c.817C>T) in the general population?

PRKCD p.Arg273Trp (c.817C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about PRKCD p.Arg273Trp (c.817C>T)?

AlphaMissense predicts likely benign (score 0.1882) — an in-silico prediction, not a clinical call.

PRKCD p.Arg273Trp

c.817C>T · rs781826732 · VCV2218258

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1882 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1882	likely benign
REVEL	0.53	indeterminate
SaProt	LLR -11.97	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 3,357 bp · p 0.00019 · regional, not allelic
Overall
CADD	31.0	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

Grpmax group 0.00329% South Asian · 3/91,072 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.00105% 17/1,613,826 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,822
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,592
South Asiangrpmax	0.00329%	30,357
Admixed American	0.00167%	59,994
African / African-American	0.00133%	74,912
European (non-Finnish)	0.000678%	147,491

Remaining individuals 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.Arg273Trp
Coding: c.817C>T
MANE Select: NM_006254
dbSNP: rs781826732
Type: single nucleotide variant
Location: chr3:53184903 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.29 · 2 PDB

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.Arg273Gln Uncertain significance ★ ⚠ 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.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-arg273trp (accessed [today's date]).

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