Is PRKD1 p.Pro45fs (c.134del) pathogenic?

PRKD1 p.Pro45fs (c.134del) is classified Uncertain significance in PRKD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-07). Very rare (popmax 0.00118%, sas); Associated with congenital heart defects and ectodermal dysplasia.

What condition is associated with PRKD1 p.Pro45fs (c.134del)?

PRKD1 p.Pro45fs (c.134del) is associated with congenital heart defects and ectodermal dysplasia (ClinVar).

How common is PRKD1 p.Pro45fs (c.134del) in the general population?

PRKD1 p.Pro45fs (c.134del) is very rare (popmax 0.00118%, sas) (gnomAD).

PRKD1 p.Pro45fs

c.134del · VCV3894551

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00118%, sas)

Conditions

congenital heart defects and ectodermal dysplasia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.94	GERP -0.85, phastCons 0.005

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00118% South Asian · 1/84,946 alleles

Filtering AF 8.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.000322% 5/1,553,176 alleles · very rare exomes 5/1,402,102 · genomes 0/151,074 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00118%	84,946
European (non-Finnish)	0.000347%	288,084

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: PRKD1
Protein: p.Pro45fs
Coding: c.134del
MANE Select: NM_002742
Type: Deletion
Location: chr14:29927379 (GRCh38)
Gene constraint: LOEUF 0.762 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.99

Full PRKD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital heart defects and ectodermal dysplasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRKD1 p.Gly676fs Likely pathogenic ★ same condition
PRKD1 p.Pro45Leu Uncertain significance ★ ⚠ same residue
PRKD1 p.Ala529Thr Uncertain significance ★★ ⚠ same condition
PRKD1 p.Arg740Gln Uncertain significance ★★ ⚠ same condition
PRKD1 p.Gln115His Uncertain significance ★★ ⚠ same condition
PRKD1 p.Gly486Arg Uncertain significance ★★ ⚠ same condition
PRKD1 p.Ser354Asn Uncertain significance ★★ ⚠ same condition
PRKD1 c.2166+39A>C Benign ★★ 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/prkd1-p-pro45fs (accessed [today's date]).

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