Is PREPL p.Arg293= (c.879G>T) pathogenic?

PREPL p.Arg293= (c.879G>T) is classified Likely benign in PREPL (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-26). Very rare (popmax 0.00237%, nfe); Associated with PREPL-related disorder.

What condition is associated with PREPL p.Arg293= (c.879G>T)?

PREPL p.Arg293= (c.879G>T) is associated with PREPL-related disorder (ClinVar).

How common is PREPL p.Arg293= (c.879G>T) in the general population?

PREPL p.Arg293= (c.879G>T) is very rare (popmax 0.00237%, nfe) (gnomAD).

PREPL p.Arg293=

c.879G>T · rs546552914 · VCV3043363

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00237%, nfe)

Conditions

PREPL-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.62	GERP -4.9, phastCons 0.015
Overall
CADD	5.139	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00237% European (non-Finnish) · 28/1,179,224 alleles

Filtering AF 0.00165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.0018% 29/1,610,674 alleles · very rare exomes 24/1,458,544 · genomes 5/152,130 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00237%	42,115
African / African-American	0.00134%	74,758

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: PREPL
Protein: p.Arg293=
Coding: c.879G>T
MANE Select: NM_001171613
dbSNP: rs546552914
Type: single nucleotide variant
Location: chr2:44338360 (GRCh38)
Gene constraint: LOEUF 1.247 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.46 · 2 PDB
Residue 293: a β-strand

Full PREPL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PREPL-related disorder

Similar variants

PREPL p.Arg293Trp Uncertain significance ★★ ⚠ same residue
PREPL p.Arg293Gln Uncertain significance ★ ⚠ same residue
PREPL p.Gln14Ter Pathogenic/Likely pathogenic ★★ same condition
PREPL p.Tyr53Ter Likely pathogenic ★ same condition
PREPL p.Gly391Glu Uncertain significance ⚠ same condition
PREPL c.1480-5T>C Likely benign same condition
PREPL c.1827+4T>C Likely benign same condition
PREPL c.-49+1660A>G Likely benign 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/prepl-p-arg293 (accessed [today's date]).

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