Is LGI1 p.Phe338= (c.1014C>T) pathogenic?

LGI1 p.Phe338= (c.1014C>T) is classified Likely benign in LGI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-12-18). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with LGI1 p.Phe338= (c.1014C>T)?

LGI1 p.Phe338= (c.1014C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LGI1 p.Phe338= (c.1014C>T) in the general population?

LGI1 p.Phe338= (c.1014C>T) is absent from gnomAD v4.1 (gnomAD).

LGI1 p.Phe338=

c.1014C>T · rs1442418989 · VCV1739313

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

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 7.7	GERP 1.9, phastCons 1
Overall
CADD	11.66	PHRED · no single calibrated threshold — expert panels disagree

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.Phe338=
Coding: c.1014C>T
MANE Select: NM_005097
dbSNP: rs1442418989
Type: single nucleotide variant
Location: chr10:93797143 (GRCh38)
Gene constraint: LOEUF 0.33 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.81 · 9 PDB
Residue 338: a UniProt-annotated variant site (in dee121; likely pathogenic; loss of protein secretion); a β-strand

Full LGI1 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

LGI1 p.Phe338Ser Pathogenic ★ same residue
LGI1 c.504-1G>T Likely pathogenic ★★ same condition
LGI1 p.Ala375Thr Uncertain significance ★★ ⚠ same condition
LGI1 p.Arg209His Uncertain significance ★★ ⚠ same condition
LGI1 p.His190Tyr Uncertain significance ★★ ⚠ same condition
LGI1 p.Ile130Met Uncertain significance ★★ ⚠ same condition
LGI1 p.Phe356Leu Uncertain significance ★★ same condition
LGI1 p.Pro91Leu 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-phe338 (accessed [today's date]).

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