Is PRX p.Lys762= (c.2286G>A) pathogenic?

PRX p.Lys762= (c.2286G>A) is classified Likely benign in PRX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-10). Very rare (popmax 0.00703%, nfe); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with PRX p.Lys762= (c.2286G>A)?

PRX p.Lys762= (c.2286G>A) is associated with Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is PRX p.Lys762= (c.2286G>A) in the general population?

PRX p.Lys762= (c.2286G>A) is very rare (popmax 0.00703%, nfe) (gnomAD).

PRX p.Lys762=

c.2286G>A · rs373111657 · VCV1086046

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00703%, nfe)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.38	GERP -4.5
Overall
CADD	1.363	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00703% European (non-Finnish) · 83/1,180,060 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00533%

Overall 0.00545% 88/1,614,102 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00703%	14,218
Admixed American	0.00333%	30,005
Remaining individualsnot grpmax-eligible	0.0032%	31,243
East Asian	0.00223%	44,900

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.Lys762=
Coding: c.2286G>A
MANE Select: NM_181882
dbSNP: rs373111657
Type: single nucleotide variant
Location: chr19:40396066 (GRCh38)
Gene constraint: LOEUF 1.321 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 35.74 · 1 PDB
Residue 762: 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.Lys762Arg Uncertain significance ★ ⚠ same residue
PRX c.184+2T>C Likely pathogenic ★★ same condition
PRX p.Arg1070Ter Pathogenic/Likely pathogenic ★★ same condition
PRX p.Arg196Ter Pathogenic/Likely pathogenic ★★ same condition
PRX p.Arg364Ter Pathogenic ★★ same condition
PRX p.Arg368Ter Pathogenic/Likely pathogenic ★★ same condition
PRX p.Arg392Ter Pathogenic/Likely pathogenic ★★ same condition
PRX p.Arg464Ter 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-lys762 (accessed [today's date]).

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