Is PRX p.Lys39fs (c.116_117del) pathogenic?

PRX p.Lys39fs (c.116117del) is classified Pathogenic in PRX (ClinVar, Single submitter, 2 submitters; last evaluated 2024-12-12). Absent from gnomAD; Associated with Charcot-Marie-Tooth disease type 4F.

What condition is associated with PRX p.Lys39fs (c.116_117del)?

PRX p.Lys39fs (c.116_117del) is associated with Charcot-Marie-Tooth disease type 4F, Charcot-Marie-Tooth disease (ClinVar).

How common is PRX p.Lys39fs (c.116_117del) in the general population?

PRX p.Lys39fs (c.116_117del) is absent from gnomAD (gnomAD).

How is Charcot-Marie-Tooth disease type 4F inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

PRX p.Lys39fs

c.116_117del · rs1599662861 · VCV637400

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Charcot-Marie-Tooth disease type 4F

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 5 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.6	GERP 0.012, 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: PRX
Protein: p.Lys39fs
Coding: c.116_117del
MANE Select: NM_181882
dbSNP: rs1599662861
Type: Deletion
Location: chr19:40403773 (GRCh38)
Gene constraint: LOEUF 1.321 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 35.74 · 1 PDB
Residue 39: the pdz domain

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

Disease context

Charcot-Marie-Tooth disease type 4F — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease

For Charcot-Marie-Tooth disease type 4F (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

PRX p.Ala210fs Pathogenic ★★ same condition
PRX p.Asp765fs Pathogenic/Likely pathogenic ★★ same condition
PRX p.Ile1096fs Pathogenic/Likely pathogenic ★★ same condition
PRX p.Thr1033fs Pathogenic/Likely pathogenic ★★ same condition
PRX p.Ala1447fs Uncertain significance ★★ same condition
PRX p.Phe94del Uncertain significance ★★ same condition
PRX p.Pro278_Ala287del Uncertain significance ★★ same condition
PRX p.Ala318fs Likely pathogenic ★ 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/prx-p-lys39fs (accessed [today's date]).

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