Is PREPL p.Lys362Arg (c.1085A>G) pathogenic?

PREPL p.Lys362Arg (c.1085A>G) is classified Uncertain significance in PREPL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). AlphaMissense: likely benign (0.0762); Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with PREPL p.Lys362Arg (c.1085A>G)?

PREPL p.Lys362Arg (c.1085A>G) is associated with Inborn genetic diseases (ClinVar).

How common is PREPL p.Lys362Arg (c.1085A>G) in the general population?

PREPL p.Lys362Arg (c.1085A>G) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about PREPL p.Lys362Arg (c.1085A>G)?

AlphaMissense predicts likely benign (score 0.0762) — an in-silico prediction, not a clinical call.

PREPL p.Lys362Arg

c.1085A>G · rs1224756167 · VCV3218546

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0762 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0762	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -7.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.21	donor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 5.1	GERP 1.7, phastCons 1
Regional constraint	o/e 1.29	unconstrained · MANE · 25 kb · p 1e-15 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM K451R vs ClinVar K362R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,014 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000124% 2/1,610,966 alleles · very rare exomes 1/1,458,768 · genomes 1/152,198 · joint denominator

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.Lys362Arg
Coding: c.1085A>G
MANE Select: NM_001171613
dbSNP: rs1224756167
Type: single nucleotide variant
Location: chr2:44332460 (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 p.Lys362Glu Uncertain significance ★ ⚠ same residue
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

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-lys362arg (accessed [today's date]).

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