Is PREPL p.Pro298Leu (c.893C>T) pathogenic?

PREPL p.Pro298Leu (c.893C>T) is classified Uncertain significance in PREPL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-12). AlphaMissense: ambiguous (0.5524); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PREPL p.Pro298Leu (c.893C>T)?

PREPL p.Pro298Leu (c.893C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PREPL p.Pro298Leu (c.893C>T) in the general population?

PREPL p.Pro298Leu (c.893C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PREPL p.Pro298Leu (c.893C>T)?

AlphaMissense predicts ambiguous (score 0.5524) — an in-silico prediction, not a clinical call.

PREPL p.Pro298Leu

c.893C>T · rs2466161182 · VCV2282952

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5524 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5524	ambiguous
REVEL	0.44	indeterminate
SaProt	LLR -10.58	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Regional constraint	o/e 1.29	unconstrained · MANE · 25 kb · p 1e-15 · regional, not allelic
Overall
CADD	28.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P387L vs ClinVar P298L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PREPL
Protein: p.Pro298Leu
Coding: c.893C>T
MANE Select: NM_001171613
dbSNP: rs2466161182
Type: single nucleotide variant
Location: chr2:44332652 (GRCh38)
Gene constraint: LOEUF 1.247 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.46 · 2 PDB

Full PREPL 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

Similar variants

PREPL c.-29A>G Uncertain significance ★★ ⚠ same condition
PREPL c.-49+1840C>T Uncertain significance ★★ ⚠ same condition
PREPL p.Ala3Thr Uncertain significance ★★ ⚠ same condition
PREPL p.Ala432Thr Uncertain significance ★★ ⚠ same condition
PREPL p.Arg174Leu Uncertain significance ★★ ⚠ same condition
PREPL p.Arg353His Uncertain significance ★★ ⚠ same condition
PREPL p.Asn152Ser Uncertain significance ★★ ⚠ same condition
PREPL p.Asp102Asn Uncertain significance ★★ ⚠ 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-pro298leu (accessed [today's date]).

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