LGI4 p.Pro52=
c.156G>A · VCV4941839
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.266%, mid)
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 -4.8 | GERP -3.4 |
| Overall | ||
| CADD | 7.906 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.266%
Middle Eastern · 16/6,014 alleles
Filtering AF
0.167%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.136%
Overall
0.00884%
140/1,582,866 alleles · rare
exomes 126/1,430,544 · genomes 14/152,322 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.266% | 376 |
| Remaining individualsnot grpmax-eligible | 0.0211% | 4,729 |
| African / African-American | 0.0187% | 5,345 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0173% | 5,770 |
| European (non-Finnish) | 0.00738% | 13,548 |
| Admixed American | 0.00559% | 17,905 |
| South Asian | 0.00231% | 43,197 |
| Finnishnot grpmax-eligible | 0.00162% | 61,716 |
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.Pro52=
- Coding
- c.156G>A
- MANE Select
- NM_139284
- Type
- single nucleotide variant
- Location
- chr19:35134525 (GRCh38)
- Gene constraint
- LOEUF 1.255 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.80
Similar variants
- LGI4 p.Pro52Leu Uncertain significance ★ ⚠ same residue
- 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
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-pro52 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown