Is PRX p.Pro1083Trp (c.3247_3248delinsTG) pathogenic?

PRX p.Pro1083Trp (c.32473248delinsTG) is classified Uncertain significance in PRX (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-26). Absent from gnomAD; Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with PRX p.Pro1083Trp (c.3247_3248delinsTG)?

PRX p.Pro1083Trp (c.3247_3248delinsTG) is associated with Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is PRX p.Pro1083Trp (c.3247_3248delinsTG) in the general population?

PRX p.Pro1083Trp (c.3247_3248delinsTG) is absent from gnomAD (gnomAD).

PRX p.Pro1083Trp

c.3247_3248delinsTG · rs2079419662 · VCV863126

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Charcot-Marie-Tooth disease type 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.8	GERP 0.63, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 2,740 bp · p 0.15 · regional, not allelic

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.Pro1083Trp
Coding: c.3247_3248delinsTG
MANE Select: NM_181882
dbSNP: rs2079419662
Type: Indel
Location: chr19:40395104 (GRCh38)
Gene constraint: LOEUF 1.321 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 35.74 · 1 PDB
Residue 1083: a UniProt-annotated variant site (in)

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

Disease context

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

Similar variants

PRX p.Pro1083Leu Uncertain significance ★★ ⚠ same residue
PRX p.Pro1083Arg Benign/Likely benign ★★ same residue
PRX p.Pro1083= Likely benign ★ same residue
PRX p.Pro1083Ser Uncertain significance ★ ⚠ same residue
PRX p.Pro575Thr Uncertain significance ★ same condition
PRX p.Val1118Ile Uncertain significance ★ same condition
PRX p.Val657Lys Uncertain significance ★ same condition
PRX c.184+2T>C 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-pro1083trp (accessed [today's date]).

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