Is PRX p.Ala342= (c.1026A>C) pathogenic?

PRX p.Ala342= (c.1026A>C) is classified Conflicting classifications of pathogenicity in PRX (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-14). Ultra-rare (popmax 0.0286%, nfe); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with PRX p.Ala342= (c.1026A>C)?

PRX p.Ala342= (c.1026A>C) is associated with Charcot-Marie-Tooth disease type 4, Charcot-Marie-Tooth disease type 4F (ClinVar).

How common is PRX p.Ala342= (c.1026A>C) in the general population?

PRX p.Ala342= (c.1026A>C) is ultra-rare (popmax 0.0286%, nfe) (gnomAD).

PRX p.Ala342=

c.1026A>C · rs150772010 · VCV476947

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0286%, 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 -4.3	GERP -4.5
Overall
CADD	1.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0286% European (non-Finnish) · 337/1,179,950 alleles

Filtering AF 0.026% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0251%

Overall 0.022% 355/1,612,996 alleles · ultra-rare exomes 335/1,460,810 · genomes 20/152,186 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0286%	3,501
Remaining individualsnot grpmax-eligible	0.0224%	4,462
African / African-American	0.004%	24,977
Admixed American	0.00167%	60,010

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.Ala342=
Coding: c.1026A>C
MANE Select: NM_181882
dbSNP: rs150772010
Type: single nucleotide variant
Location: chr19:40397326 (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 type 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease type 4F

Similar variants

PRX p.Ala342Thr 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-ala342 (accessed [today's date]).

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