Is LGI1 p.Phe314= (c.942T>C) pathogenic?

LGI1 p.Phe314= (c.942T>C) is classified Likely benign in LGI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-24). Very rare (popmax 0.000424%, nfe); Associated with autosomal dominant epilepsy with auditory features.

What condition is associated with LGI1 p.Phe314= (c.942T>C)?

LGI1 p.Phe314= (c.942T>C) is associated with autosomal dominant epilepsy with auditory features (ClinVar).

How common is LGI1 p.Phe314= (c.942T>C) in the general population?

LGI1 p.Phe314= (c.942T>C) is very rare (popmax 0.000424%, nfe) (gnomAD).

How is Epilepsy with auditory features inherited?

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

LGI1 p.Phe314=

c.942T>C · rs2134026268 · VCV1650738

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Conditions

autosomal dominant epilepsy with auditory features

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 0.53	GERP -0.72, phastCons 1
Overall
CADD	8.228	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,584 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,613,334 alleles · very rare exomes 5/1,460,990 · genomes 0/152,344 · 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: LGI1
Protein: p.Phe314=
Coding: c.942T>C
MANE Select: NM_005097
dbSNP: rs2134026268
Type: single nucleotide variant
Location: chr10:93797071 (GRCh38)
Gene constraint: LOEUF 0.33 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.81 · 9 PDB
Residue 314: a UniProt-annotated variant site (in dee121; likely pathogenic; loss of protein secretion); a turn

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.Phe314Tyr Uncertain significance ★ ⚠ same residue
LGI1 p.Phe314fs Pathogenic ★ 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

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-phe314 (accessed [today's date]).

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