Is LGI1 p.Pro15Arg (c.44C>G) pathogenic?

LGI1 p.Pro15Arg (c.44C>G) is classified Uncertain significance in LGI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-06). AlphaMissense: likely benign (0.0901); Absent from gnomAD v4.1; Associated with autosomal dominant epilepsy with auditory features.

What condition is associated with LGI1 p.Pro15Arg (c.44C>G)?

LGI1 p.Pro15Arg (c.44C>G) is associated with autosomal dominant epilepsy with auditory features (ClinVar).

How common is LGI1 p.Pro15Arg (c.44C>G) in the general population?

LGI1 p.Pro15Arg (c.44C>G) is absent from gnomAD v4.1 (gnomAD).

How is Epilepsy with auditory features inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about LGI1 p.Pro15Arg (c.44C>G)?

AlphaMissense predicts likely benign (score 0.0901) — an in-silico prediction, not a clinical call.

LGI1 p.Pro15Arg

c.44C>G · rs1554901888 · VCV2134620

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0901 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal dominant epilepsy with auditory features

Computational evidence

Protein change
AlphaMissense	0.0901	likely benign
REVEL	0.231	benign-leaning
SaProt	LLR -5.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 161 bp · p 0.63 · regional, not allelic
Overall
CADD	20.9	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.

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: LGI1
Protein: p.Pro15Arg
Coding: c.44C>G
MANE Select: NM_005097
dbSNP: rs1554901888
Type: single nucleotide variant
Location: chr10:93758188 (GRCh38)
Gene constraint: LOEUF 0.33 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.81 · 9 PDB

Full LGI1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal dominant epilepsy with auditory features — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Epilepsy with auditory features (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

LGI1 p.Pro15Ser Uncertain significance ★ ⚠ same residue
LGI1 c.504-1G>T Likely pathogenic ★★ same condition
LGI1 p.Arg136Trp Pathogenic/Likely pathogenic ★★ same condition
LGI1 p.Arg330Ter Pathogenic ★★ same condition
LGI1 p.Arg474Gln Likely pathogenic ★★ ⚠ same condition
LGI1 p.Ser473Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
LGI1 p.Ala227Val Uncertain significance ★★ ⚠ same condition
LGI1 p.Ala253Thr 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/lgi1-p-pro15arg (accessed [today's date]).

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