Is PRX p.Ala944= (c.2832T>C) pathogenic?

PRX p.Ala944= (c.2832T>C) is classified Conflicting classifications of pathogenicity in PRX (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-19). Rare (popmax 0.179%, afr); Associated with Inborn genetic diseases.

What condition is associated with PRX p.Ala944= (c.2832T>C)?

PRX p.Ala944= (c.2832T>C) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 4F, Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is PRX p.Ala944= (c.2832T>C) in the general population?

PRX p.Ala944= (c.2832T>C) is rare (popmax 0.179%, afr) (gnomAD).

PRX p.Ala944=

c.2832T>C · rs145226687 · VCV386663

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.179%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.55	GERP -2.3, phastCons 0.59
Overall
CADD	5.539	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.179% African / African-American · 134/75,040 alleles

Filtering AF 0.154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.145%

Overall 0.00855% 138/1,614,162 alleles · rare exomes 71/1,461,892 · genomes 67/152,270 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.179%	560
Remaining individualsnot grpmax-eligible	0.0032%	31,255
Admixed American	0.00167%	60,024
European (non-Finnish)	8.47e-05%	1,180,012

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.Ala944=
Coding: c.2832T>C
MANE Select: NM_181882
dbSNP: rs145226687
Type: single nucleotide variant
Location: chr19:40395520 (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 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-ala944 (accessed [today's date]).

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