Is PRX p.Ala823= (c.2469G>A) pathogenic?

PRX p.Ala823= (c.2469G>A) is classified Benign/Likely benign in PRX (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-27). Low-frequency (popmax 2.11%, afr); Associated with Inborn genetic diseases.

What condition is associated with PRX p.Ala823= (c.2469G>A)?

PRX p.Ala823= (c.2469G>A) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 4F, Charcot-Marie-Tooth disease (ClinVar).

How common is PRX p.Ala823= (c.2469G>A) in the general population?

PRX p.Ala823= (c.2469G>A) is low-frequency (popmax 2.11%, afr) (gnomAD).

PRX p.Ala823=

c.2469G>A · rs61733450 · VCV378435

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.11%, 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 -3.2	GERP -4.2
Overall
CADD	0.493	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.11% African / African-American · 1,586/75,042 alleles

Filtering AF 2.03% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.99%

Overall 0.123% 1,983/1,614,198 alleles · low-frequency exomes 1,093/1,461,870 · genomes 890/152,328 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.11%	47
Remaining individualsnot grpmax-eligible	0.149%	672
Finnishnot grpmax-eligible	0.114%	877
Admixed American	0.113%	883
Middle Eastern	0.066%	1,516
European (non-Finnish)	0.0131%	7,613
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
East Asian	0.00223%	44,890
South Asian	0.0022%	45,543

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.Ala823=
Coding: c.2469G>A
MANE Select: NM_181882
dbSNP: rs61733450
Type: single nucleotide variant
Location: chr19:40395883 (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.Ala823Val Uncertain significance ★★ ⚠ 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-ala823 (accessed [today's date]).

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