Is PRKD1 p.Leu725Phe (c.2173C>T) pathogenic?

PRKD1 p.Leu725Phe (c.2173C>T) is classified Uncertain significance in PRKD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-16). AlphaMissense: likely pathogenic (0.9842); Absent from gnomAD v4.1.

How common is PRKD1 p.Leu725Phe (c.2173C>T) in the general population?

PRKD1 p.Leu725Phe (c.2173C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRKD1 p.Leu725Phe (c.2173C>T)?

AlphaMissense predicts likely pathogenic (score 0.9842) — an in-silico prediction, not a clinical call.

PRKD1 p.Leu725Phe

c.2173C>T · rs2502443964 · VCV1712698

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9842 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9842	likely pathogenic
REVEL	0.853	moderately pathogenic-leaning
SaProt	LLR -14.10	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 6.4, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 86 kb · p 2.8e-05 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRKD1
Protein: p.Leu725Phe
Coding: c.2173C>T
MANE Select: NM_002742
dbSNP: rs2502443964
Type: single nucleotide variant
Location: chr14:29597752 (GRCh38)
Gene constraint: LOEUF 0.762 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.99
Residue 725: the protein kinase domain

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-leu725phe (accessed [today's date]).

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