Is PRX p.Phe799Leu (c.2395T>C) pathogenic?

PRX p.Phe799Leu (c.2395T>C) is classified Uncertain significance in PRX (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-07-05). AlphaMissense: likely pathogenic (0.7462); Very rare (popmax 0.00161%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PRX p.Phe799Leu (c.2395T>C)?

PRX p.Phe799Leu (c.2395T>C) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is PRX p.Phe799Leu (c.2395T>C) in the general population?

PRX p.Phe799Leu (c.2395T>C) is very rare (popmax 0.00161%, nfe) (gnomAD).

What do computational predictors say about PRX p.Phe799Leu (c.2395T>C)?

AlphaMissense predicts likely pathogenic (score 0.7462) — an in-silico prediction, not a clinical call.

PRX p.Phe799Leu

c.2395T>C · rs372370577 · VCV1416858

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7462 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7462	likely pathogenic · top 6% in PRX
REVEL	0.017	moderately benign-leaning
SaProt	LLR -5.90	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.3	GERP 0.11, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 2,740 bp · p 0.15 · regional, not allelic
Overall
CADD	16.8	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 0.00161% European (non-Finnish) · 19/1,180,050 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.0013% 21/1,614,030 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00161%	62,108
Remaining individualsnot grpmax-eligible	0.0016%	62,486
Finnishnot grpmax-eligible	0.00156%	63,968

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.Phe799Leu
Coding: c.2395T>C
MANE Select: NM_181882
dbSNP: rs372370577
Type: single nucleotide variant
Location: chr19:40395957 (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 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-phe799leu (accessed [today's date]).

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