Is LGI1 p.Pro115Ser (c.343C>T) pathogenic?

LGI1 p.Pro115Ser (c.343C>T) is classified Uncertain significance in LGI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-09-20). AlphaMissense: likely benign (0.1843); Absent from gnomAD v4.1.

How common is LGI1 p.Pro115Ser (c.343C>T) in the general population?

LGI1 p.Pro115Ser (c.343C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LGI1 p.Pro115Ser (c.343C>T)?

AlphaMissense predicts likely benign (score 0.1843) — an in-silico prediction, not a clinical call.

LGI1 p.Pro115Ser

c.343C>T · rs1554905042 · VCV452032

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1843 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1843	likely benign
REVEL	0.249	benign-leaning
SaProt	LLR -5.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.21	donor loss · deltas
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 34 kb · p 1.5e-10 · regional, not allelic
Overall
CADD	21.4	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.Pro115Ser
Coding: c.343C>T
MANE Select: NM_005097
dbSNP: rs1554905042
Type: single nucleotide variant
Location: chr10:93777434 (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

Similar variants

LGI1 p.Pro115Leu Uncertain significance ★★ ⚠ same residue
LGI1 p.Pro115= Conflicting classifications of pathogenicity ★ same residue
LGI1 c.504-1G>T Likely pathogenic ★★ same type
LGI1 p.Arg136Trp Pathogenic/Likely pathogenic ★★ same type
LGI1 p.Arg311Ter Likely pathogenic ★★ same type
LGI1 p.Arg330Ter Pathogenic ★★ same type
LGI1 p.Arg474Gln Likely pathogenic ★★ ⚠ same type
LGI1 p.Ser473Leu Pathogenic/Likely pathogenic ★★ ⚠ same type

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-pro115ser (accessed [today's date]).

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