Is PRKD1 p.Pro620fs (c.1857dup) pathogenic?

PRKD1 p.Pro620fs (c.1857dup) is classified Uncertain significance in PRKD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-01). Ultra-rare (popmax 0.0406%, eas).

How common is PRKD1 p.Pro620fs (c.1857dup) in the general population?

PRKD1 p.Pro620fs (c.1857dup) is ultra-rare (popmax 0.0406%, eas) (gnomAD).

PRKD1 p.Pro620fs

c.1857dup · rs1197728416 · VCV3368509

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0406%, eas)

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 13 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.1, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0406% East Asian · 18/44,380 alleles

Filtering AF 0.0261% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0216%

Overall 0.00112% 18/1,604,828 alleles · ultra-rare exomes 17/1,452,730 · genomes 1/152,098 · joint denominator

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.Pro620fs
Coding: c.1857dup
MANE Select: NM_002742
dbSNP: rs1197728416
Type: Duplication
Location: chr14:29624199 (GRCh38)
Gene constraint: LOEUF 0.762 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.99
Residue 620: the protein kinase domain

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

Similar variants

PRKD1 p.Arg203fs Uncertain significance ★ same type
PRKD1 p.Ser31_Gly32dup Benign ★ same type

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-pro620fs (accessed [today's date]).

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