LGI4 p.Arg165=
c.495C>T · rs748017557 · VCV762454
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00238%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.20 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.23 | gain · loss 0.21 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -6 | GERP -3.4 |
| Overall | ||
| CADD | 4.675 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00238%
South Asian · 2/84,052 alleles
Filtering AF
0.000981%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000809%
Overall
0.00135%
21/1,551,152 alleles · very rare
exomes 20/1,398,932 · genomes 1/152,220 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00238% | 42,026 |
| Remaining individualsnot grpmax-eligible | 0.00166% | 60,086 |
| European (non-Finnish) | 0.00157% | 63,718 |
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.Arg165=
- Coding
- c.495C>T
- MANE Select
- NM_139284
- dbSNP
- rs748017557
- Type
- single nucleotide variant
- Location
- chr19:35131519 (GRCh38)
- Gene constraint
- LOEUF 1.255 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.80
- Residue 165
- the lrrct domain
Similar variants
- LGI4 p.Arg165Cys Uncertain significance ★★ ⚠ same residue
- LGI4 p.Arg165His Uncertain significance ★ ⚠ same residue
- 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
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-arg165 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown