Is LGI4 p.Asp93= (c.279C>T) pathogenic?

LGI4 p.Asp93= (c.279C>T) is classified Benign/Likely benign in LGI4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-28). Rare (popmax 0.847%, afr).

How common is LGI4 p.Asp93= (c.279C>T) in the general population?

LGI4 p.Asp93= (c.279C>T) is rare (popmax 0.847%, afr) (gnomAD).

LGI4 p.Asp93=

c.279C>T · rs148508572 · VCV733247

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.847%, afr)

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 -2.9	GERP -4.3
Overall
CADD	0.861	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.847% African / African-American · 635/74,960 alleles

Filtering AF 0.793% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.771%

Overall 0.0462% 744/1,609,688 alleles · rare exomes 358/1,457,440 · genomes 386/152,248 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.847%	118
Admixed American	0.0857%	1,166
Remaining individualsnot grpmax-eligible	0.0626%	1,598
Middle Eastern	0.0171%	5,854
South Asian	0.00446%	22,432
European (non-Finnish)	0.00119%	84,172

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.Asp93=
Coding: c.279C>T
MANE Select: NM_139284
dbSNP: rs148508572
Type: single nucleotide variant
Location: chr19:35133728 (GRCh38)
Gene constraint: LOEUF 1.255 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.80

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-asp93 (accessed [today's date]).

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