Is PRKD1 p.Pro5= (c.15G>A) pathogenic?

PRKD1 p.Pro5= (c.15G>A) is classified Likely benign in PRKD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Common (popmax 6.69%, afr) — too common for a highly-penetrant pathogenic allele.

PRKD1 p.Pro5=

Q: How common is PRKD1 p.Pro5= (c.15G>A) in the general population?

PRKD1 p.Pro5= (c.15G>A) is common (popmax 6.69%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.15G>A · rs191667643 · VCV768645

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 6.69%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP 2, phastCons 0.98
Overall
CADD	13.96	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.69% African / African-American · 4,154/62,090 alleles

Filtering AF 6.52% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.45%

Overall 0.461% 5,540/1,201,984 alleles · common exomes 2,500/1,052,994 · genomes 3,040/148,990 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.69%	15
Middle Eastern	1.41%	71
Admixed American	1.36%	74
Remaining individualsnot grpmax-eligible	0.703%	142
Ashkenazi Jewishnot grpmax-eligible	0.228%	439
European (non-Finnish)	0.072%	1,390
South Asian	0.012%	8,327
East Asian	0.00361%	27,738

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.Pro5=
Coding: c.15G>A
MANE Select: NM_002742
dbSNP: rs191667643
Type: single nucleotide variant
Location: chr14:29927498 (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

Similar variants

PRKD1 p.Ala529Thr Uncertain significance ★★ ⚠ same type
PRKD1 p.Arg201Trp Uncertain significance ★★ same type
PRKD1 p.Arg203Lys Uncertain significance ★★ ⚠ same type
PRKD1 p.Arg740Gln Uncertain significance ★★ ⚠ same type
PRKD1 p.Asn498Ser Uncertain significance ★★ ⚠ same type
PRKD1 p.Gln115His Uncertain significance ★★ ⚠ same type
PRKD1 p.Gly486Arg Uncertain significance ★★ ⚠ same type
PRKD1 p.Met424Val Uncertain significance ★★ ⚠ 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-pro5 (accessed [today's date]).

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