Is PRX p.Arg167Pro (c.500G>C) pathogenic?

PRX p.Arg167Pro (c.500G>C) is classified Uncertain significance in PRX (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-05-05). AlphaMissense: likely benign (0.3218); Ultra-rare (popmax 0.0135%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PRX p.Arg167Pro (c.500G>C)?

PRX p.Arg167Pro (c.500G>C) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 4F, Charcot-Marie-Tooth disease (ClinVar).

How common is PRX p.Arg167Pro (c.500G>C) in the general population?

PRX p.Arg167Pro (c.500G>C) is ultra-rare (popmax 0.0135%, nfe) (gnomAD).

What do computational predictors say about PRX p.Arg167Pro (c.500G>C)?

AlphaMissense predicts likely benign (score 0.3218) — an in-silico prediction, not a clinical call.

PRX p.Arg167Pro

c.500G>C · rs757322355 · VCV329286

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.3218 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0135%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3218	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -6.19	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.2, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.97 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0135% European (non-Finnish) · 159/1,175,664 alleles

Filtering AF 0.0118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0111%

Overall 0.0103% 165/1,603,548 alleles · ultra-rare exomes 155/1,451,330 · genomes 10/152,218 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0135%	7,394
Remaining individualsnot grpmax-eligible	0.00967%	10,342

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.Arg167Pro
Coding: c.500G>C
MANE Select: NM_181882
dbSNP: rs757322355
Type: single nucleotide variant
Location: chr19:40397852 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

PRX p.Arg167His Uncertain significance ★★ ⚠ same residue
PRX p.Arg167Cys Conflicting classifications of pathogenicity ★ ⚠ 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

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-arg167pro (accessed [today's date]).

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