Is LGI4 p.Ser471= (c.1413C>T) pathogenic?

LGI4 p.Ser471= (c.1413C>T) is classified Benign in LGI4 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-12-28). Ultra-rare (popmax 0.087%, eas).

How common is LGI4 p.Ser471= (c.1413C>T) in the general population?

LGI4 p.Ser471= (c.1413C>T) is ultra-rare (popmax 0.087%, eas) (gnomAD).

LGI4 p.Ser471=

c.1413C>T · rs568391550 · VCV799487

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.087%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.4	GERP -4.5
Overall
CADD	3.856	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.087% East Asian · 39/44,802 alleles

Filtering AF 0.0654% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0579%

Overall 0.00434% 70/1,612,106 alleles · ultra-rare exomes 64/1,459,768 · genomes 6/152,338 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.087%	1,149
Remaining individualsnot grpmax-eligible	0.0032%	31,205
European (non-Finnish)	0.00229%	43,667
Admixed American	0.00167%	59,712
South Asian	0.0011%	90,940

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: LGI4
Protein: p.Ser471=
Coding: c.1413C>T
MANE Select: NM_139284
dbSNP: rs568391550
Type: single nucleotide variant
Location: chr19:35125394 (GRCh38)
Gene constraint: LOEUF 1.255 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.80
Residue 471: a UniProt-annotated variant site (in amc1)

Full LGI4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LGI4 p.Arg165Cys Uncertain significance ★★ ⚠ same type
LGI4 p.Asp438Val Uncertain significance ★★ ⚠ same type
LGI4 p.Leu211Gln Uncertain significance ★★ ⚠ same type
LGI4 p.Leu315Gln Uncertain significance ★★ ⚠ same type
LGI4 c.1299+221A>G Benign ★★ same type
LGI4 c.1299+52T>C Benign ★★ same type
LGI4 c.1300-134C>T Benign ★★ same type
LGI4 c.1300-151G>C Benign ★★ 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/lgi4-p-ser471 (accessed [today's date]).

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