Is PRKD3 p.Asp368Val (c.1103A>T) pathogenic?

PRKD3 p.Asp368Val (c.1103A>T) is classified Uncertain significance in PRKD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-30). AlphaMissense: likely benign (0.1678); Very rare (popmax 0.00314%, nfe).

How common is PRKD3 p.Asp368Val (c.1103A>T) in the general population?

PRKD3 p.Asp368Val (c.1103A>T) is very rare (popmax 0.00314%, nfe) (gnomAD).

What do computational predictors say about PRKD3 p.Asp368Val (c.1103A>T)?

AlphaMissense predicts likely benign (score 0.1678) — an in-silico prediction, not a clinical call.

PRKD3 p.Asp368Val

c.1103A>T · VCV4144516

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1678 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00314%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1678	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -7.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.53 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 47 kb · p 0.51 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00314% European (non-Finnish) · 37/1,179,972 alleles

Filtering AF 0.00231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00242% 39/1,613,952 alleles · very rare exomes 33/1,461,718 · genomes 6/152,234 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00314%	31,891
African / African-American	0.00267%	37,516

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: PRKD3
Protein: p.Asp368Val
Coding: c.1103A>T
MANE Select: NM_005813
Type: single nucleotide variant
Location: chr2:37279815 (GRCh38)
Gene constraint: LOEUF 0.682 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.57 · 1 PDB
Residue 368: the 'disordered' region

Full PRKD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRKD3 p.Ala3Ser Uncertain significance ★ ⚠ same type
PRKD3 p.Ala511Gly Uncertain significance ★ ⚠ same type
PRKD3 p.Ala530Gly Uncertain significance ★ ⚠ same type
PRKD3 p.Arg211His Uncertain significance ★ ⚠ same type
PRKD3 p.Arg211Leu Uncertain significance ★ ⚠ same type
PRKD3 p.Arg297Cys Uncertain significance ★ ⚠ same type
PRKD3 p.Arg355Gln Uncertain significance ★ ⚠ same type
PRKD3 p.Arg429Met 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/prkd3-p-asp368val (accessed [today's date]).

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