LAMC3 p.Ser1364=
c.4092C>T · rs141724499 · VCV195884
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 9 submitters
gnomAD v4.1
Rare
rare (popmax 0.633%, nfe)
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 -2.2 | GERP -3.1 |
| Overall | ||
| CADD | 3.418 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.633%
European (non-Finnish) · 7,466/1,180,028 alleles
Filtering AF
0.621%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.616%
Overall
0.542%
8,750/1,614,078 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.633% | 158 |
| Remaining individualsnot grpmax-eligible | 0.626% | 160 |
| South Asian | 0.542% | 184 |
| Middle Eastern | 0.462% | 216 |
| Ashkenazi Jewishnot grpmax-eligible | 0.318% | 315 |
| Admixed American | 0.265% | 377 |
| Amishnot grpmax-eligible | 0.11% | 912 |
| African / African-American | 0.0986% | 1,014 |
| Finnishnot grpmax-eligible | 0.0657% | 1,523 |
| East Asian | 0.00223% | 44,878 |
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.Ser1364=
- Coding
- c.4092C>T
- MANE Select
- NM_006059
- dbSNP
- rs141724499
- Type
- single nucleotide variant
- Location
- chr9:131085585 (GRCh38)
- Gene constraint
- LOEUF 0.909 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.23
- Residue 1364
- the 'domain ii and i' region
Similar variants
- LAMC3 p.Ser1364Cys Uncertain significance ★ ⚠ same residue
- 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
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-ser1364 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown