Is PDK3 p.Arg162= (c.486C>T) pathogenic?

PDK3 p.Arg162= (c.486C>T) is classified Likely benign in PDK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-23). Very rare (popmax 0.000791%, nfe); Associated with Charcot-Marie-Tooth disease X-linked dominant 6.

What condition is associated with PDK3 p.Arg162= (c.486C>T)?

PDK3 p.Arg162= (c.486C>T) is associated with Charcot-Marie-Tooth disease X-linked dominant 6 (ClinVar).

How common is PDK3 p.Arg162= (c.486C>T) in the general population?

PDK3 p.Arg162= (c.486C>T) is very rare (popmax 0.000791%, nfe) (gnomAD).

How is X-linked Charcot-Marie-Tooth disease type 6 inherited?

Typically X-linked dominant (Orphanet). A genetic counselor can assess individual risk for a family.

PDK3 p.Arg162=

c.486C>T · rs1479754596 · VCV648471

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000791%, nfe)

Conditions

Charcot-Marie-Tooth disease X-linked dominant 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.12	GERP -1.2, phastCons 0.93
Overall
CADD	7.469	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000791% European (non-Finnish) · 7/884,647 alleles

Filtering AF 0.000329% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000212%

Overall 0.000588% 7/1,190,693 alleles · very rare exomes 6/1,078,291 · genomes 1/112,402 · 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: PDK3
Protein: p.Arg162=
Coding: c.486C>T
MANE Select: NM_005391
dbSNP: rs1479754596
Type: single nucleotide variant
Location: chrX:24503492 (GRCh38)
Structure: AlphaFold pLDDT 91.32 · 5 PDB
Residue 162: the histidine kinase domain; an α-helix

Full PDK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease X-linked dominant 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked Charcot-Marie-Tooth disease type 6 (Orphanet):

Inheritance: X-linked dominant
Onset: Childhood

Similar variants

PDK3 p.Arg162His Conflicting classifications of pathogenicity ★ ⚠ same residue
PDK3 c.320+6T>C Uncertain significance ★★ same condition
PDK3 p.Ala360Val Uncertain significance ★★ ⚠ same condition
PDK3 p.Arg378Cys Uncertain significance ★★ same condition
PDK3 p.Asp188Asn Uncertain significance ★★ ⚠ same condition
PDK3 p.Ile113Thr Uncertain significance ★★ ⚠ same condition
PDK3 p.Leu112Pro Uncertain significance ★★ ⚠ same condition
PDK3 p.Pro141Leu Uncertain significance ★★ ⚠ same condition

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/pdk3-p-arg162 (accessed [today's date]).

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