LAMB3 p.Ser733=
c.2199C>T · rs748747266 · VCV1124307
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
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 -7.2 | GERP -3.6 |
| Overall | ||
| CADD | 2.263 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/60,008 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.00192%
31/1,614,062 alleles · very rare
exomes 28/1,461,850 · genomes 3/152,212 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.005% | 20,003 |
| South Asian | 0.00329% | 30,362 |
| European (non-Finnish) | 0.00186% | 53,638 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
| Finnishnot grpmax-eligible | 0.00156% | 64,010 |
| African / African-American | 0.00133% | 74,944 |
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.Ser733=
- Coding
- c.2199C>T
- MANE Select
- NM_000228
- dbSNP
- rs748747266
- Type
- single nucleotide variant
- Location
- chr1:209623664 (GRCh38)
- Gene constraint
- LOEUF 0.829 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.55
- Residue 733
- the 'domain ii' region
Similar variants
- LAMB3 p.Ser733Phe Uncertain significance ★ ⚠ 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-ser733 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown