Is PRX p.Pro513= (c.1539G>A) pathogenic?

PRX p.Pro513= (c.1539G>A) is classified Benign/Likely benign in PRX (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-19). Rare (popmax 0.176%, sas); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with PRX p.Pro513= (c.1539G>A)?

PRX p.Pro513= (c.1539G>A) is associated with Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is PRX p.Pro513= (c.1539G>A) in the general population?

PRX p.Pro513= (c.1539G>A) is rare (popmax 0.176%, sas) (gnomAD).

PRX p.Pro513=

c.1539G>A · rs187786861 · VCV698518

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.176%, sas)

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 -1.7	GERP -2.2
Overall
CADD	0.021	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.176% South Asian · 160/90,668 alleles

Filtering AF 0.154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.146%

Overall 0.0119% 191/1,610,422 alleles · rare exomes 171/1,460,938 · genomes 20/149,484 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.176%	567
Middle Eastern	0.0331%	3,019
East Asian	0.0179%	5,574
Remaining individualsnot grpmax-eligible	0.0144%	6,933
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,783
African / African-American	0.00405%	24,663
Admixed American	0.00335%	29,835
European (non-Finnish)	0.000424%	235,782

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.Pro513=
Coding: c.1539G>A
MANE Select: NM_181882
dbSNP: rs187786861
Type: single nucleotide variant
Location: chr19:40396813 (GRCh38)
Gene constraint: LOEUF 1.321 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 35.74 · 1 PDB
Residue 513: the '55 x 5 aa approximate tandem repeats of [lvmag]-[psreqc]-[edkl]-[livmap]-[aqkhrpe]; that may have a tripeptide spacer of [lv]-p-[ker]' 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 p.Pro513Leu 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-pro513 (accessed [today's date]).

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