Is PRX p.Arg679Ter (c.2035C>T) pathogenic?

PRX p.Arg679Ter (c.2035C>T) is classified Uncertain significance in PRX (ClinVar, Single submitter, 3 submitters; last evaluated 2023-06-22). Ultra-rare (popmax 0.0178%, eas); Associated with Charcot-Marie-Tooth disease type 4F.

What condition is associated with PRX p.Arg679Ter (c.2035C>T)?

PRX p.Arg679Ter (c.2035C>T) is associated with Charcot-Marie-Tooth disease type 4F, Charcot-Marie-Tooth disease type 3 (ClinVar).

How common is PRX p.Arg679Ter (c.2035C>T) in the general population?

PRX p.Arg679Ter (c.2035C>T) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

How is Charcot-Marie-Tooth disease type 4F inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

PRX p.Arg679Ter

c.2035C>T · rs1469912467 · VCV637481

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Conditions

Charcot-Marie-Tooth disease type 4F

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (7 of 7) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.34	GERP 1.5
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% East Asian · 8/44,826 alleles

Filtering AF 0.00884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00062% 10/1,612,038 alleles · ultra-rare exomes 9/1,461,038 · genomes 1/151,000 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,603
South Asian	0.0011%	91,032
European (non-Finnish)	8.48e-05%	1,179,778

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.Arg679Ter
Coding: c.2035C>T
MANE Select: NM_181882
dbSNP: rs1469912467
Type: single nucleotide variant
Location: chr19:40396317 (GRCh38)
Gene constraint: LOEUF 1.321 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 35.74 · 1 PDB
Residue 679: 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 4F — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease type 3

For Charcot-Marie-Tooth disease type 4F (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

PRX p.Arg679Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
PRX p.Arg679= Likely benign ★ same residue
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-arg679ter (accessed [today's date]).

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