Is PRX p.Asp79= (c.237C>T) pathogenic?

PRX p.Asp79= (c.237C>T) is classified Conflicting classifications of pathogenicity in PRX (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-11-01). Ultra-rare (popmax 0.0165%, mid); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with PRX p.Asp79= (c.237C>T)?

PRX p.Asp79= (c.237C>T) is associated with Charcot-Marie-Tooth disease type 4, Charcot-Marie-Tooth disease type 4F (ClinVar).

How common is PRX p.Asp79= (c.237C>T) in the general population?

PRX p.Asp79= (c.237C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

PRX p.Asp79=

c.237C>T · rs376174896 · VCV329290

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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	GERP -2.3
Overall
CADD	10.28	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00286%

Overall 0.00378% 61/1,614,108 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,400
Remaining individualsnot grpmax-eligible	0.0064%	15,625
European (non-Finnish)	0.00415%	24,081
Admixed American	0.00333%	30,016
African / African-American	0.00133%	75,034

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.Asp79=
Coding: c.237C>T
MANE Select: NM_181882
dbSNP: rs376174896
Type: single nucleotide variant
Location: chr19:40398764 (GRCh38)
Gene constraint: LOEUF 1.321 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 35.74 · 1 PDB
Residue 79: the pdz domain; an α-helix

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

Also linked: Charcot-Marie-Tooth disease type 4F

Similar variants

PRX p.Asp79Val 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-asp79 (accessed [today's date]).

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