Is PRX p.Ile42fs (c.124_125insGCTGC) pathogenic?

PRX p.Ile42fs (c.124125insGCTGC) is classified Pathogenic in PRX (ClinVar, Single submitter, 1 submitter). No gnomAD frequency available for this variant; Associated with Charcot-Marie-Tooth disease.

What condition is associated with PRX p.Ile42fs (c.124_125insGCTGC)?

PRX p.Ile42fs (c.124_125insGCTGC) is associated with Charcot-Marie-Tooth disease (ClinVar).

How common is PRX p.Ile42fs (c.124_125insGCTGC) in the general population?

PRX p.Ile42fs (c.124_125insGCTGC) is no gnomAD frequency available for this variant (gnomAD).

PRX p.Ile42fs

c.124_125insGCTGC · rs2079512634 · VCV916817

Pathogenic Single submitter

Classification

Pathogenic

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

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 11	GERP 2.3, 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.Ile42fs
Coding: c.124_125insGCTGC
MANE Select: NM_181882
dbSNP: rs2079512634
Type: Insertion
Location: chr19:40403765 (GRCh38)
Gene constraint: LOEUF 1.321 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 35.74 · 1 PDB
Residue 42: the pdz domain; a β-strand

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

Disease context

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

Similar variants

PRX p.Glu40_Gly41insGluAlaAlaArg Pathogenic ★ same condition
PRX p.Arg196Ter Pathogenic/Likely pathogenic ★★ same condition
PRX p.Arg364Ter Pathogenic ★★ same condition
PRX p.Arg953Ter Pathogenic ★★ same condition
PRX p.Cys715Ter Pathogenic/Likely pathogenic ★★ same condition
PRX p.Gln60fs Pathogenic/Likely pathogenic ★★ same condition
PRX p.Gln622Ter Pathogenic/Likely pathogenic ★★ same condition
PRX p.Glu197Ter Pathogenic/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-ile42fs (accessed [today's date]).

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