L1CAM p.Ala1237=
c.3711G>A · rs782576787 · VCV589105
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00653%, amr)
Conditions
1
Spastic paraplegia
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 -7.8 | GERP -3.7 |
| Overall | ||
| CADD | 0.118 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00653%
Admixed American · 3/45,976 alleles
Filtering AF
0.00173%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00088%
Overall
0.000743%
9/1,211,001 alleles · very rare
exomes 8/1,098,083 · genomes 1/112,918 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00653% | 15,325 |
| South Asian | 0.00351% | 28,467 |
| East Asian | 0.00296% | 33,783 |
| European (non-Finnish) | 0.000335% | 298,432 |
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
- L1CAM
- Protein
- p.Ala1237=
- Coding
- c.3711G>A
- MANE Select
- NM_001278116
- dbSNP
- rs782576787
- Type
- single nucleotide variant
- Location
- chrX:153862726 (GRCh38)
- Structure
- AlphaFold pLDDT 78.82 · 2 PDB
- Residue 1237
- a UniProt-annotated variant site (found in l1 syndrome; likely pathogenic); the 'disordered' region
Similar variants
- L1CAM p.Ala1237Val Benign/Likely benign ★★ same residue
- L1CAM c.2431+5G>A Pathogenic/Likely pathogenic ★★ same condition
- L1CAM c.2872+1G>A Pathogenic ★★ same condition
- L1CAM c.3531-12G>A Pathogenic/Likely pathogenic ★★ same condition
- L1CAM c.400+5G>A Pathogenic/Likely pathogenic ★★ same condition
- L1CAM c.806+1G>C Pathogenic ★★ same condition
- L1CAM c.807-6G>A Pathogenic/Likely pathogenic ★★ same condition
- L1CAM c.92-1G>A Pathogenic/Likely pathogenic ★★ same condition
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/l1cam-p-ala1237 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown