Is PRX p.Pro278= (c.834G>A) pathogenic?

PRX p.Pro278= (c.834G>A) is classified Likely benign in PRX (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-03). Very rare (popmax 0.00488%, nfe); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with PRX p.Pro278= (c.834G>A)?

PRX p.Pro278= (c.834G>A) is associated with Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is PRX p.Pro278= (c.834G>A) in the general population?

PRX p.Pro278= (c.834G>A) is very rare (popmax 0.00488%, nfe) (gnomAD).

PRX p.Pro278=

c.834G>A · rs759984063 · VCV1159410

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00488%, 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 -7.1	GERP -3.7
Overall
CADD	0.167	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00488% European (non-Finnish) · 56/1,147,842 alleles

Filtering AF 0.00385% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00346%

Overall 0.00407% 63/1,546,772 alleles · very rare exomes 61/1,394,540 · genomes 2/152,232 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00488%	20,497
African / African-American	0.0041%	24,391
Remaining individualsnot grpmax-eligible	0.00333%	30,014
South Asian	0.00236%	42,401

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.Pro278=
Coding: c.834G>A
MANE Select: NM_181882
dbSNP: rs759984063
Type: single nucleotide variant
Location: chr19:40397518 (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

Similar variants

PRX p.Pro278Leu Uncertain significance ★★ ⚠ same residue
PRX p.Pro278_Ala287del 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

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-pro278 (accessed [today's date]).

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