LAMC3 p.Cys336=
c.1008C>T · rs143784718 · VCV510055
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.167%, 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 -1.9 | GERP 1.9 |
| Overall | ||
| CADD | 3.44 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.167%
African / African-American · 125/75,056 alleles
Filtering AF
0.143%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.134%
Overall
0.00849%
137/1,613,370 alleles · rare
exomes 63/1,461,072 · genomes 74/152,298 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.167% | 600 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,929 |
| Admixed American | 0.00833% | 12,004 |
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
- LAMC3
- Protein
- p.Cys336=
- Coding
- c.1008C>T
- MANE Select
- NM_006059
- dbSNP
- rs143784718
- Type
- single nucleotide variant
- Location
- chr9:131038895 (GRCh38)
- Gene constraint
- LOEUF 0.909 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.23
- Residue 336
- a disulfide bond; the laminin egf-like 2 domain
Similar variants
- LAMC3 c.1166-1G>A Likely pathogenic ★★ same type
- LAMC3 c.3211+1G>A Likely pathogenic ★★ same type
- LAMC3 c.3211+2T>C Likely pathogenic ★★ same type
- LAMC3 c.976+1G>A Pathogenic ★★ same type
- LAMC3 p.Cys810Ter Pathogenic ★★ same type
- LAMC3 p.Gln550Ter Pathogenic ★★ same type
- LAMC3 p.Ser421Ter Pathogenic ★★ same type
- LAMC3 p.Ala1090Ser Uncertain significance ★★ ⚠ 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/lamc3-p-cys336 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown