Is PRX p.Arg392fs (c.1173del) pathogenic?

PRX p.Arg392fs (c.1173del) is classified Pathogenic in PRX (ClinVar, No assertion criteria, 1 submitter). Very rare (popmax 0.00668%, afr); Associated with Charcot-Marie-Tooth disease.

What condition is associated with PRX p.Arg392fs (c.1173del)?

PRX p.Arg392fs (c.1173del) is associated with Charcot-Marie-Tooth disease (ClinVar).

How common is PRX p.Arg392fs (c.1173del) in the general population?

PRX p.Arg392fs (c.1173del) is very rare (popmax 0.00668%, afr) (gnomAD).

PRX p.Arg392fs

c.1173del · rs757771239 · VCV637391

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

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	escapes	premature termination codon in the last exon (7 of 7) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.5	GERP 1.1, phastCons 1
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% African / African-American · 5/74,884 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.00031% 5/1,613,826 alleles · very rare exomes 1/1,461,784 · genomes 4/152,042 · 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: PRX
Protein: p.Arg392fs
Coding: c.1173del
MANE Select: NM_181882
dbSNP: rs757771239
Type: Deletion
Location: chr19:40397179 (GRCh38)
Gene constraint: LOEUF 1.321 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 35.74 · 1 PDB

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.Arg392Ter Pathogenic/Likely pathogenic ★★ same residue
PRX p.Ile1096fs 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.Gly41fs Likely pathogenic ★ same condition
PRX p.Lys39fs Pathogenic ★ same condition
PRX p.Val112_Ser113del 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/prx-p-arg392fs (accessed [today's date]).

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