Is PRX p.Lys930fs (c.2787del) pathogenic?

PRX p.Lys930fs (c.2787del) is classified Pathogenic/Likely pathogenic in PRX (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-08-18). Ultra-rare (popmax 0.0383%, amr); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with PRX p.Lys930fs (c.2787del)?

PRX p.Lys930fs (c.2787del) is associated with Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is PRX p.Lys930fs (c.2787del) in the general population?

PRX p.Lys930fs (c.2787del) is ultra-rare (popmax 0.0383%, amr) (gnomAD).

PRX p.Lys930fs

c.2787del · rs754521978 · VCV217239

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0383%, amr)

Conditions

Charcot-Marie-Tooth disease type 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	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 · substitutions only
Constraint at this position
Conservation	phyloP 5.1	GERP 2.3, phastCons 1
Overall
CADD	28.4	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 0.0383% Admixed American · 23/59,992 alleles

Filtering AF 0.0261% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0222%

Overall 0.00155% 25/1,614,040 alleles · ultra-rare exomes 24/1,461,894 · genomes 1/152,146 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0383%	2,608
Remaining individualsnot grpmax-eligible	0.0032%	31,244

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.Lys930fs
Coding: c.2787del
MANE Select: NM_181882
dbSNP: rs754521978
Type: Deletion
Location: chr19:40395565 (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.Lys930Asn Uncertain significance ★★ ⚠ same residue
PRX p.Ala210fs Pathogenic ★★ same condition
PRX p.Asp765fs Pathogenic/Likely pathogenic ★★ same condition
PRX p.Ile1096fs Pathogenic/Likely pathogenic ★★ same condition
PRX p.Thr1033fs Pathogenic/Likely pathogenic ★★ same condition
PRX p.Val525fs Pathogenic/Likely pathogenic ★★ same condition
PRX p.629MKLPE[1] Uncertain significance ★★ same condition
PRX p.Ala1447fs Uncertain significance ★★ 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-lys930fs (accessed [today's date]).

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