Is PRX p.Ala244= (c.732G>A) pathogenic?

PRX p.Ala244= (c.732G>A) is classified Conflicting classifications of pathogenicity in PRX (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-09-28). Ultra-rare (popmax 0.0121%, eas); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with PRX p.Ala244= (c.732G>A)?

PRX p.Ala244= (c.732G>A) is associated with Charcot-Marie-Tooth disease type 4, Charcot-Marie-Tooth disease type 4F (ClinVar).

How common is PRX p.Ala244= (c.732G>A) in the general population?

PRX p.Ala244= (c.732G>A) is ultra-rare (popmax 0.0121%, eas) (gnomAD).

PRX p.Ala244=

c.732G>A · rs769735682 · VCV698970

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, 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 -9.6	GERP -4.5
Overall
CADD	0.545	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0121% East Asian · 5/41,346 alleles

Filtering AF 0.00475% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00306%

Overall 0.00195% 30/1,541,540 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0121%	8,269
Admixed American	0.00975%	10,254
African / African-American	0.00545%	18,360
Remaining individualsnot grpmax-eligible	0.00167%	60,048
European (non-Finnish)	0.00122%	82,067
South Asian	0.00119%	84,336

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.Ala244=
Coding: c.732G>A
MANE Select: NM_181882
dbSNP: rs769735682
Type: single nucleotide variant
Location: chr19:40397620 (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

Also linked: Charcot-Marie-Tooth disease type 4F

Similar variants

PRX p.Ala244Val Benign/Likely benign ★★ same residue
PRX p.Ala244Glu Uncertain significance ★ ⚠ same residue
PRX p.Ala244Ser Uncertain significance ★ ⚠ same residue
PRX p.Ala244Thr 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

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-ala244 (accessed [today's date]).

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