LAMC2 p.Arg685=
c.2055G>A · rs140057433 · VCV763836
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0187%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.94 | GERP -0.22, phastCons 0.92 |
| Overall | ||
| CADD | 7.284 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0187%
African / African-American · 14/75,002 alleles
Filtering AF
0.0112%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00904%
Overall
0.00118%
19/1,613,546 alleles · ultra-rare
exomes 7/1,461,276 · genomes 12/152,270 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0187% | 5,357 |
| Admixed American | 0.00333% | 30,007 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,452 |
| European (non-Finnish) | 0.00017% | 589,967 |
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
- LAMC2
- Protein
- p.Arg685=
- Coding
- c.2055G>A
- MANE Select
- NM_005562
- dbSNP
- rs140057433
- Type
- single nucleotide variant
- Location
- chr1:183232692 (GRCh38)
- Gene constraint
- LOEUF 0.797 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 72.89
- Residue 685
- the 'domain ii and i' region
Similar variants
- LAMC2 c.1715-2A>G Likely pathogenic ★★ same type
- LAMC2 c.268+1G>A Likely pathogenic ★★ same type
- LAMC2 c.3328+1G>A Pathogenic/Likely pathogenic ★★ same type
- LAMC2 c.640+1G>A Likely pathogenic ★★ same type
- LAMC2 p.Arg1129Ter Pathogenic ★★ same type
- LAMC2 p.Arg115Ter Pathogenic ★★ same type
- LAMC2 p.Arg170Ter Pathogenic/Likely pathogenic ★★ same type
- LAMC2 p.Arg223Ter 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/lamc2-p-arg685 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown