PRX p.Pro549=
c.1647G>A · rs202113722 · VCV2158143
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0202%, eas)
Conditions
1
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 -20 | GERP -2.6 |
| Overall | ||
| CADD | 2.259 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0202%
East Asian · 9/44,652 alleles
Filtering AF
0.0104%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00783%
Overall
0.00124%
20/1,610,224 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0202% | 4,961 |
| South Asian | 0.0044% | 22,718 |
| African / African-American | 0.00271% | 36,865 |
| European (non-Finnish) | 0.000424% | 235,777 |
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.Pro549=
- Coding
- c.1647G>A
- MANE Select
- NM_181882
- dbSNP
- rs202113722
- Type
- single nucleotide variant
- Location
- chr19:40396705 (GRCh38)
- Gene constraint
- LOEUF 1.321 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 35.74 · 1 PDB
- Residue 549
- 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
Similar variants
- PRX p.Pro549Leu Uncertain significance ★★ ⚠ same residue
- PRX p.Pro549Arg Uncertain significance ★ ⚠ same residue
- PRX p.Pro549Ser 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
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-pro549 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown