Is PRX p.Arg970Trp (c.2908C>T) pathogenic?

PRX p.Arg970Trp (c.2908C>T) is classified Uncertain significance in PRX (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-05-22). AlphaMissense: likely benign (0.1538); Very rare (popmax 0.00668%, afr); Associated with Charcot-Marie-Tooth disease.

What condition is associated with PRX p.Arg970Trp (c.2908C>T)?

PRX p.Arg970Trp (c.2908C>T) is associated with Charcot-Marie-Tooth disease, Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is PRX p.Arg970Trp (c.2908C>T) in the general population?

PRX p.Arg970Trp (c.2908C>T) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about PRX p.Arg970Trp (c.2908C>T)?

AlphaMissense predicts likely benign (score 0.1538) — an in-silico prediction, not a clinical call.

PRX p.Arg970Trp

c.2908C>T · rs369224308 · VCV917238

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1538 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Charcot-Marie-Tooth disease

Computational evidence

Protein change
AlphaMissense	0.1538	likely benign
REVEL	0.189	benign-leaning
SaProt	LLR -10.29	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP -0.014, phastCons 0.95
Regional constraint	o/e 0.96	unconstrained · MANE · 2,740 bp · p 0.15 · regional, not allelic
Overall
CADD	22.1	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 0.00668% African / African-American · 5/74,862 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.00204% 33/1,613,852 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,972
Remaining individualsnot grpmax-eligible	0.0048%	20,827
South Asian	0.00329%	30,357
European (non-Finnish)	0.00186%	53,637

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.Arg970Trp
Coding: c.2908C>T
MANE Select: NM_181882
dbSNP: rs369224308
Type: single nucleotide variant
Location: chr19:40395444 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease type 4

Similar variants

PRX p.Arg970Gln Uncertain significance ★★ ⚠ same residue
PRX p.Arg970= Likely benign ★ 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-arg970trp (accessed [today's date]).

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