LAMB1 p.Val680=
c.2040G>A · rs139446144 · VCV1640420
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0893%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.20 | donor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP 1.2, phastCons 1 |
| Overall | ||
| CADD | 14.65 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0893%
African / African-American · 67/75,012 alleles
Filtering AF
0.0721%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0659%
Overall
0.00508%
82/1,614,092 alleles · ultra-rare
exomes 42/1,461,864 · genomes 40/152,228 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0893% | 1,120 |
| Admixed American | 0.0117% | 8,575 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,626 |
| European (non-Finnish) | 0.000339% | 295,002 |
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
- LAMB1
- Protein
- p.Val680=
- Coding
- c.2040G>A
- MANE Select
- NM_002291
- dbSNP
- rs139446144
- Type
- single nucleotide variant
- Location
- chr7:107961275 (GRCh38)
- Gene constraint
- LOEUF 0.601 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.99 · 3 PDB
- Residue 680
- the laminin iv type b domain
Similar variants
- LAMB1 c.4188+1G>C Pathogenic/Likely pathogenic ★★ same type
- LAMB1 p.Arg397Ter Pathogenic ★★ same type
- LAMB1 p.Gln577Ter Pathogenic ★★ same type
- LAMB1 c.1985+5G>T Uncertain significance ★★ same type
- LAMB1 c.4746-3C>A Uncertain significance ★★ same type
- LAMB1 p.Ala1069Val Uncertain significance ★★ ⚠ same type
- LAMB1 p.Ala1239Thr Uncertain significance ★★ ⚠ same type
- LAMB1 p.Ala1331Gly 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/lamb1-p-val680 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown