Is PRX p.Lys718Glu (c.2152A>G) pathogenic?

PRX p.Lys718Glu (c.2152A>G) is classified Uncertain significance in PRX (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: likely benign (0.1805); Very rare (popmax 0.00168%, amr); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with PRX p.Lys718Glu (c.2152A>G)?

PRX p.Lys718Glu (c.2152A>G) is associated with Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is PRX p.Lys718Glu (c.2152A>G) in the general population?

PRX p.Lys718Glu (c.2152A>G) is very rare (popmax 0.00168%, amr) (gnomAD).

What do computational predictors say about PRX p.Lys718Glu (c.2152A>G)?

AlphaMissense predicts likely benign (score 0.1805) — an in-silico prediction, not a clinical call.

PRX p.Lys718Glu

c.2152A>G · rs2079433906 · VCV953325

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1805 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00168%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Charcot-Marie-Tooth disease type 4

Computational evidence

Protein change
AlphaMissense	0.1805	likely benign
REVEL	0.12	moderately benign-leaning
SaProt	LLR -10.90	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP 1.4, phastCons 0.98
Regional constraint	o/e 0.96	unconstrained · MANE · 2,740 bp · p 0.15 · regional, not allelic
Overall
CADD	20.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00168% Admixed American · 1/59,590 alleles

Overall 6.84e-05% 1/1,461,568 alleles · very rare

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.Lys718Glu
Coding: c.2152A>G
MANE Select: NM_181882
dbSNP: rs2079433906
Type: single nucleotide variant
Location: chr19:40396200 (GRCh38)
Gene constraint: LOEUF 1.321 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 35.74 · 1 PDB
Residue 718: 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 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
PRX p.Arg897Ter 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-lys718glu (accessed [today's date]).

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