Is PRX p.Ala53Asp (c.158C>A) pathogenic?

PRX p.Ala53Asp (c.158C>A) is classified Uncertain significance in PRX (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-07-08). AlphaMissense: likely pathogenic (0.9938); Absent from gnomAD v4.1; Associated with Charcot-Marie-Tooth disease.

What condition is associated with PRX p.Ala53Asp (c.158C>A)?

PRX p.Ala53Asp (c.158C>A) is associated with Charcot-Marie-Tooth disease, Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is PRX p.Ala53Asp (c.158C>A) in the general population?

PRX p.Ala53Asp (c.158C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRX p.Ala53Asp (c.158C>A)?

AlphaMissense predicts likely pathogenic (score 0.9938) — an in-silico prediction, not a clinical call.

PRX p.Ala53Asp

c.158C>A · rs753322071 · VCV916923

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9938 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,566,802)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Charcot-Marie-Tooth disease

Computational evidence

Protein change
AlphaMissense	0.9938	likely pathogenic · top 1% in PRX
REVEL	0.473	indeterminate
SaProt	LLR -12.63	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.97 · regional, not allelic
Overall
CADD	30.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,566,802). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PRX
Protein: p.Ala53Asp
Coding: c.158C>A
MANE Select: NM_181882
dbSNP: rs753322071
Type: single nucleotide variant
Location: chr19:40403732 (GRCh38)
Gene constraint: LOEUF 1.321 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 35.74 · 1 PDB
Residue 53: 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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease type 4

Similar variants

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
PRX p.Arg897Ter 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-ala53asp (accessed [today's date]).

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