Is PDK3 p.Pro54fs (c.149_158dup) pathogenic?

PDK3 p.Pro54fs (c.149158dup) is classified Uncertain significance in PDK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-30). No gnomAD frequency available for this variant; Associated with Charcot-Marie-Tooth disease X-linked dominant 6.

What condition is associated with PDK3 p.Pro54fs (c.149_158dup)?

PDK3 p.Pro54fs (c.149_158dup) is associated with Charcot-Marie-Tooth disease X-linked dominant 6 (ClinVar).

How common is PDK3 p.Pro54fs (c.149_158dup) in the general population?

PDK3 p.Pro54fs (c.149_158dup) is no gnomAD frequency available for this variant (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.Pro54fs

c.149_158dup · rs2518575057 · VCV2119685

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP 2.5, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PDK3
Protein: p.Pro54fs
Coding: c.149_158dup
MANE Select: NM_005391
dbSNP: rs2518575057
Type: Duplication
Location: chrX:24494783 (GRCh38)
Structure: AlphaFold pLDDT 91.32 · 5 PDB
Residue 54: 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.Pro54Ser Uncertain significance ★ ⚠ same residue
PDK3 c.249-9dup Benign/Likely benign ★★ same condition
PDK3 c.106+14_106+15dup Uncertain significance ★ same condition
PDK3 p.Ser363fs Uncertain significance ★ same condition
PDK3 p.Ter407ValextTer? Uncertain significance ★ same condition
PDK3 c.1078-3_1078-2dup Likely benign ★ same condition
PDK3 c.320+6T>C Uncertain significance ★★ same condition
PDK3 p.Ala360Val 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-pro54fs (accessed [today's date]).

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