Is PRX p.Val657Lys (c.1969_1970delinsAA) pathogenic?

PRX p.Val657Lys (c.19691970delinsAA) is classified Uncertain significance in PRX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-20). Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with PRX p.Val657Lys (c.1969_1970delinsAA)?

PRX p.Val657Lys (c.1969_1970delinsAA) is associated with Charcot-Marie-Tooth disease type 4 (ClinVar).

PRX p.Val657Lys

c.1969_1970delinsAA · VCV3707081

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

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 7.6	GERP 0.52, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 2,740 bp · p 0.15 · regional, not allelic
Region caveats
Repeat context	tandem	AGACTTTCGGCAGCTGCACCTCCGGGAGGTGCACATCGGGCACAGCCATCTCAGGCACCTTAGGGAGTTTCATCTCTG simple repeat · ambiguous alignment · confidence, not pathogenicity

Variant & gene context

Gene: PRX
Protein: p.Val657Lys
Coding: c.1969_1970delinsAA
MANE Select: NM_181882
Type: Indel
Location: chr19:40396382 (GRCh38)
Gene constraint: LOEUF 1.321 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 35.74 · 1 PDB
Residue 657: the '55 x 5 aa approximate tandem repeats of [lvmag]-[psreqc]-[edkl]-[livmap]-[aqkhrpe]; that may have a tripeptide spacer of [lv]-p-[ker]' region

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.Val657= Likely benign ★ same residue
PRX p.Pro1083Trp Uncertain significance ★ same condition
PRX p.Pro575Thr Uncertain significance ★ same condition
PRX p.Val1118Ile Uncertain significance ★ same condition
PRX p.Val657Gly Uncertain significance ★ ⚠ same residue
PRX c.184+2T>C Likely pathogenic ★★ same condition
PRX p.Ala210fs Pathogenic ★★ same condition
PRX p.Arg1070Ter 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-val657lys (accessed [today's date]).

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