LAMC3 p.Pro622=
c.1866C>G · rs537785027 · VCV391765
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00666%, 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 0.28 | GERP -0.27, phastCons 0.94 |
| Overall | ||
| CADD | 4.86 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00666%
African / African-American · 5/75,062 alleles
Filtering AF
0.00255%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00161%
Overall
0.000496%
8/1,614,022 alleles · very rare
exomes 4/1,461,674 · genomes 4/152,348 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00666% | 15,012 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,252 |
| Admixed American | 0.00167% | 60,036 |
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.Pro622=
- Coding
- c.1866C>G
- MANE Select
- NM_006059
- dbSNP
- rs537785027
- Type
- single nucleotide variant
- Location
- chr9:131052892 (GRCh38)
- Gene constraint
- LOEUF 0.909 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.23
- Residue 622
- the laminin iv type a domain
Similar variants
- LAMC3 p.Pro622His Uncertain significance ★★ ⚠ same residue
- LAMC3 p.Pro622Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
- LAMC3 p.Pro622Leu 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
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-pro622 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown