Is PRX p.Asp155Val (c.464A>T) pathogenic?

PRX p.Asp155Val (c.464A>T) is classified Uncertain significance in PRX (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-07-23). AlphaMissense: likely pathogenic (0.8869); Very rare (popmax 0.000594%, nfe); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with PRX p.Asp155Val (c.464A>T)?

PRX p.Asp155Val (c.464A>T) is associated with Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is PRX p.Asp155Val (c.464A>T) in the general population?

PRX p.Asp155Val (c.464A>T) is very rare (popmax 0.000594%, nfe) (gnomAD).

What do computational predictors say about PRX p.Asp155Val (c.464A>T)?

AlphaMissense predicts likely pathogenic (score 0.8869) — an in-silico prediction, not a clinical call.

PRX p.Asp155Val

c.464A>T · rs2079458431 · VCV972632

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8869 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000594%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Charcot-Marie-Tooth disease type 4

Computational evidence

Protein change
AlphaMissense	0.8869	likely pathogenic · top 3% in PRX
REVEL	0.184	benign-leaning
SaProt	LLR -7.06	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.4, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.97 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000594% European (non-Finnish) · 7/1,179,004 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,611,702 alleles · very rare exomes 7/1,459,454 · genomes 0/152,248 · joint denominator

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.Asp155Val
Coding: c.464A>T
MANE Select: NM_181882
dbSNP: rs2079458431
Type: single nucleotide variant
Location: chr19:40397888 (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 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-asp155val (accessed [today's date]).

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