Is PRX p.Ala1320= (c.3960C>T) pathogenic?

PRX p.Ala1320= (c.3960C>T) is classified Likely benign in PRX (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-17). Rare (popmax 0.138%, afr); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with PRX p.Ala1320= (c.3960C>T)?

PRX p.Ala1320= (c.3960C>T) is associated with Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is PRX p.Ala1320= (c.3960C>T) in the general population?

PRX p.Ala1320= (c.3960C>T) is rare (popmax 0.138%, afr) (gnomAD).

PRX p.Ala1320=

c.3960C>T · rs149626915 · VCV1150669

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.138%, afr)

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 -5.9	GERP -3.4
Overall
CADD	0.484	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.138% African / African-American · 103/74,562 alleles

Filtering AF 0.117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.108%

Overall 0.00781% 125/1,600,118 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.138%	724
Middle Eastern	0.0165%	6,044
Admixed American	0.0103%	9,689
Remaining individualsnot grpmax-eligible	0.00485%	20,635
European (non-Finnish)	0.00102%	97,787

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.Ala1320=
Coding: c.3960C>T
MANE Select: NM_181882
dbSNP: rs149626915
Type: single nucleotide variant
Location: chr19:40394392 (GRCh38)
Gene constraint: LOEUF 1.321 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 35.74 · 1 PDB
Residue 1320: the 'disordered' 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-ala1320 (accessed [today's date]).

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