Is PRX p.Ala1384= (c.4152G>A) pathogenic?

PRX p.Ala1384= (c.4152G>A) is classified Likely benign in PRX (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-24). Ultra-rare (popmax 0.0335%, mid); Associated with Inborn genetic diseases.

What condition is associated with PRX p.Ala1384= (c.4152G>A)?

PRX p.Ala1384= (c.4152G>A) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is PRX p.Ala1384= (c.4152G>A) in the general population?

PRX p.Ala1384= (c.4152G>A) is ultra-rare (popmax 0.0335%, mid) (gnomAD).

PRX p.Ala1384=

c.4152G>A · rs756887163 · VCV389318

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0335%, mid)

Conditions

Inborn genetic diseases

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 -4.7	GERP -3.1
Overall
CADD	0.032	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0335% Middle Eastern · 2/5,964 alleles

Filtering AF 0.00591% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00245%

Overall 0.00245% 39/1,591,022 alleles · ultra-rare exomes 35/1,438,876 · genomes 4/152,146 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0335%	2,982
Ashkenazi Jewishnot grpmax-eligible	0.00353%	28,318
European (non-Finnish)	0.00292%	34,278
East Asian	0.00225%	44,502
Finnishnot grpmax-eligible	0.00158%	63,430

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.Ala1384=
Coding: c.4152G>A
MANE Select: NM_181882
dbSNP: rs756887163
Type: single nucleotide variant
Location: chr19:40394200 (GRCh38)
Gene constraint: LOEUF 1.321 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 35.74 · 1 PDB
Residue 1384: the 'disordered' region

Full PRX gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease type 4

Similar variants

PRX p.Ala1384Val 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-ala1384 (accessed [today's date]).

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