Is PRX p.Pro214= (c.642C>G) pathogenic?

PRX p.Pro214= (c.642C>G) is classified Likely benign in PRX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). Very rare (popmax 0.00117%, sas); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with PRX p.Pro214= (c.642C>G)?

PRX p.Pro214= (c.642C>G) is associated with Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is PRX p.Pro214= (c.642C>G) in the general population?

PRX p.Pro214= (c.642C>G) is very rare (popmax 0.00117%, sas) (gnomAD).

PRX p.Pro214=

c.642C>G · rs551628239 · VCV2727758

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00117%, 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 -3.2	GERP -4.5
Overall
CADD	1.019	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00117% South Asian · 1/85,620 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000437%

Overall 0.000833% 13/1,561,428 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00117%	85,620
European (non-Finnish)	0.00104%	96,469

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.Pro214=
Coding: c.642C>G
MANE Select: NM_181882
dbSNP: rs551628239
Type: single nucleotide variant
Location: chr19:40397710 (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

Similar variants

PRX p.Pro214Arg Uncertain significance ★★ ⚠ same residue
PRX p.Pro214His Uncertain significance ★★ ⚠ same residue
PRX p.Pro214Leu 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-pro214 (accessed [today's date]).

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