LAMB3 p.Ala129=
c.387C>T · rs374988953 · VCV794988
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0801%, 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 -7.3 | GERP -3.8 |
| Overall | ||
| CADD | 0.642 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0801%
African / African-American · 60/74,900 alleles
Filtering AF
0.0638%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.058%
Overall
0.00533%
86/1,613,216 alleles · ultra-rare
exomes 51/1,461,150 · genomes 35/152,066 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0801% | 1,248 |
| Admixed American | 0.00334% | 29,970 |
| European (non-Finnish) | 0.00187% | 53,618 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,444 |
| South Asian | 0.0011% | 90,982 |
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
- LAMB3
- Protein
- p.Ala129=
- Coding
- c.387C>T
- MANE Select
- NM_000228
- dbSNP
- rs374988953
- Type
- single nucleotide variant
- Location
- chr1:209634624 (GRCh38)
- Gene constraint
- LOEUF 0.829 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.55
- Residue 129
- the laminin n-terminal domain
Similar variants
- LAMB3 p.Ala129fs Likely pathogenic ★ same residue
- LAMB3 c.1132+5G>A Pathogenic/Likely pathogenic ★★ same type
- LAMB3 c.1133-22G>A Pathogenic ★★ same type
- LAMB3 c.1288+1G>T Pathogenic/Likely pathogenic ★★ same type
- LAMB3 c.1486-1G>A Likely pathogenic ★★ same type
- LAMB3 c.1597+1G>T Likely pathogenic ★★ same type
- LAMB3 c.2138-1G>A Likely pathogenic ★★ same type
- LAMB3 c.2701+2T>C Likely 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/lamb3-p-ala129 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown