Is PRX p.Pro780= (c.2340G>A) pathogenic?

PRX p.Pro780= (c.2340G>A) is classified Likely benign in PRX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-09). Ultra-rare (popmax 0.0174%, afr); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with PRX p.Pro780= (c.2340G>A)?

PRX p.Pro780= (c.2340G>A) is associated with Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is PRX p.Pro780= (c.2340G>A) in the general population?

PRX p.Pro780= (c.2340G>A) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

PRX p.Pro780=

c.2340G>A · rs147618050 · VCV732601

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

Conditions

Charcot-Marie-Tooth disease type 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Overall
CADD	6.395	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0174% African / African-American · 13/74,896 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00813%

Overall 0.00136% 22/1,613,870 alleles · ultra-rare exomes 14/1,461,702 · genomes 8/152,168 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0174%	5,761
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
South Asian	0.0011%	91,092
European (non-Finnish)	0.000593%	168,578

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.Pro780=
Coding: c.2340G>A
MANE Select: NM_181882
dbSNP: rs147618050
Type: single nucleotide variant
Location: chr19:40396012 (GRCh38)
Gene constraint: LOEUF 1.321 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 35.74 · 1 PDB
Residue 780: 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.Pro780Leu 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-pro780 (accessed [today's date]).

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