LAMB3 p.Phe139=
c.417C>T · rs201554705 · VCV755404
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.23 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.3 | GERP -4.1 |
| Overall | ||
| CADD | 6.727 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,082 alleles
Filtering AF
0.00226%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00135%
Overall
0.00167%
27/1,613,966 alleles · ultra-rare
exomes 25/1,461,866 · genomes 2/152,100 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,082 |
| Admixed American | 0.00667% | 15,000 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,827 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,598 |
| East Asian | 0.00223% | 44,852 |
| African / African-American | 0.00133% | 74,908 |
| European (non-Finnish) | 0.00127% | 78,668 |
| South Asian | 0.0011% | 91,084 |
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.Phe139=
- Coding
- c.417C>T
- MANE Select
- NM_000228
- dbSNP
- rs201554705
- Type
- single nucleotide variant
- Location
- chr1:209634594 (GRCh38)
- Gene constraint
- LOEUF 0.829 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.55
- Residue 139
- the laminin n-terminal domain
Similar variants
- 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
- LAMB3 c.28+1G>T 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-phe139 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown