Is PRX p.Ser1439= (c.4317C>T) pathogenic?

PRX p.Ser1439= (c.4317C>T) is classified Conflicting classifications of pathogenicity in PRX (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-03-08). Very rare (popmax 0.00892%, eas); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with PRX p.Ser1439= (c.4317C>T)?

PRX p.Ser1439= (c.4317C>T) is associated with Charcot-Marie-Tooth disease type 4, Charcot-Marie-Tooth disease type 4F (ClinVar).

How common is PRX p.Ser1439= (c.4317C>T) in the general population?

PRX p.Ser1439= (c.4317C>T) is very rare (popmax 0.00892%, eas) (gnomAD).

PRX p.Ser1439=

c.4317C>T · rs372280596 · VCV416225

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

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 -5.2	GERP -3.4
Overall
CADD	0.126	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00892% East Asian · 4/44,868 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00273% 44/1,613,140 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,217
South Asian	0.00549%	18,210
European (non-Finnish)	0.00288%	34,691
Admixed American	0.00167%	59,936

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.Ser1439=
Coding: c.4317C>T
MANE Select: NM_181882
dbSNP: rs372280596
Type: single nucleotide variant
Location: chr19:40394035 (GRCh38)
Gene constraint: LOEUF 1.321 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 35.74 · 1 PDB
Residue 1439: the 'disordered' region; a modified residue (phosphoserine)

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.Ser1439Arg Uncertain significance ★★ ⚠ same residue
PRX p.Ser1439Ile 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-ser1439 (accessed [today's date]).

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