Is PRKD1 p.Leu7Pro (c.20T>C) pathogenic?

PRKD1 p.Leu7Pro (c.20T>C) is classified Likely benign in PRKD1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-05-01). AlphaMissense: likely benign (0.0941); Rare (popmax 0.978%, nfe).

How common is PRKD1 p.Leu7Pro (c.20T>C) in the general population?

PRKD1 p.Leu7Pro (c.20T>C) is rare (popmax 0.978%, nfe) (gnomAD).

What do computational predictors say about PRKD1 p.Leu7Pro (c.20T>C)?

AlphaMissense predicts likely benign (score 0.0941) — an in-silico prediction, not a clinical call.

PRKD1 p.Leu7Pro

c.20T>C · rs572057574 · VCV789329

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0941 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.978%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0941	likely benign
REVEL	0.083	moderately benign-leaning
SaProt	LLR -4.42	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 3.5	GERP 1.3, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 108 bp · p 0.0049 · regional, not allelic
Overall
CADD	21.0	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 0.978% European (non-Finnish) · 9,591/980,870 alleles

Filtering AF 0.961% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.955%

Overall 0.844% 10,261/1,215,328 alleles · rare exomes 9,413/1,067,312 · genomes 848/148,016 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.978%	102
Admixed American	0.796%	126
Remaining individualsnot grpmax-eligible	0.705%	142
African / African-American	0.152%	658
Finnishnot grpmax-eligible	0.149%	672
Middle Eastern	0.128%	780
Ashkenazi Jewishnot grpmax-eligible	0.118%	846
South Asian	0.0744%	1,343

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.Leu7Pro
Coding: c.20T>C
MANE Select: NM_002742
dbSNP: rs572057574
Type: single nucleotide variant
Location: chr14:29927493 (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-leu7pro (accessed [today's date]).

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