Is PRX p.Val882Ala (c.2645T>C) pathogenic?

PRX p.Val882Ala (c.2645T>C) is classified Benign in PRX (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0514); Common (popmax 80%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Charcot-Marie-Tooth disease.

What condition is associated with PRX p.Val882Ala (c.2645T>C)?

PRX p.Val882Ala (c.2645T>C) is associated with Charcot-Marie-Tooth disease, Charcot-Marie-Tooth disease type 3, Charcot-Marie-Tooth disease type 4F (ClinVar).

What do computational predictors say about PRX p.Val882Ala (c.2645T>C)?

AlphaMissense predicts likely benign (score 0.0514) — an in-silico prediction, not a clinical call.

PRX p.Val882Ala

Q: How common is PRX p.Val882Ala (c.2645T>C) in the general population?

PRX p.Val882Ala (c.2645T>C) is common (popmax 80%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2645T>C · rs268671 · VCV130048

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

AlphaMissense

likely benign

0.0514 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 80%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Charcot-Marie-Tooth disease

Computational evidence

Protein change
AlphaMissense	0.0514	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -5.59	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 3.8	GERP -3.9, phastCons 0.74
Regional constraint	o/e 0.96	unconstrained · MANE · 2,740 bp · p 0.15 · regional, not allelic
Overall
CADD	2.165	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 80% African / African-American · 59,918/74,852 alleles

Filtering AF 79.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 79.3%

Overall 52.6% 849,154/1,613,456 alleles · common exomes 761,420/1,461,798 · genomes 87,734/151,658 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	80%	1
Amishnot grpmax-eligible	65.3%	2
European (non-Finnish)	53.3%	2
Admixed American	51.9%	2
Remaining individualsnot grpmax-eligible	51.5%	2
South Asian	47.1%	2
Ashkenazi Jewishnot grpmax-eligible	46.1%	2
Middle Eastern	44.9%	2
Finnishnot grpmax-eligible	44.9%	2
East Asian	18.6%	5

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.Val882Ala
Coding: c.2645T>C
MANE Select: NM_181882
dbSNP: rs268671
Type: single nucleotide variant
Location: chr19:40395707 (GRCh38)
Gene constraint: LOEUF 1.321 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 35.74 · 1 PDB
Residue 882: a UniProt-annotated variant site (in)

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 3 Charcot-Marie-Tooth disease type 4F Charcot-Marie-Tooth disease type 4

Similar variants

PRX p.Val882= 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
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-val882ala (accessed [today's date]).

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