ESAM p.Leu13=
c.37C>T · VCV4533509
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.159%, nfe)
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 4.7 | GERP 0.74, phastCons 1 |
| Overall | ||
| CADD | 8.752 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.159%
European (non-Finnish) · 1,869/1,177,704 alleles
Filtering AF
0.153%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.15%
Overall
0.124%
1,998/1,609,398 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.159% | 630 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0885% | 1,130 |
| Remaining individualsnot grpmax-eligible | 0.061% | 1,640 |
| Admixed American | 0.0552% | 1,812 |
| Finnishnot grpmax-eligible | 0.0313% | 3,196 |
| African / African-American | 0.0161% | 6,207 |
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
- ESAM
- Protein
- p.Leu13=
- Coding
- c.37C>T
- MANE Select
- NM_138961
- Type
- single nucleotide variant
- Location
- chr11:124762118 (GRCh38)
- Gene constraint
- LOEUF 1.009 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.13
- Residue 13
- a UniProt-annotated variant site (in nedihss)
Similar variants
- ESAM p.Val149Ala Uncertain significance ★★ ⚠ same type
- ESAM c.731-9C>A Benign ★★ same type
- ESAM p.Arg107Trp Likely benign ★★ ⚠ same type
- ESAM p.Ile290Val Likely benign ★★ same type
- ESAM p.Leu31= Likely benign ★★ same type
- ESAM p.Pro181= Likely benign ★★ same type
- ESAM c.451+1G>A Likely pathogenic ★ same type
- ESAM c.608-1G>A 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/esam-p-leu13 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown