ESAM p.Pro26=
c.78C>A · VCV4681525
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.111%, afr)
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 -0.89 | GERP -1.3 |
| Overall | ||
| CADD | 7.891 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.111%
African / African-American · 82/73,572 alleles
Filtering AF
0.092%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0848%
Overall
0.00726%
113/1,556,402 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.111% | 897 |
| Admixed American | 0.0272% | 3,678 |
| Middle Eastern | 0.0178% | 5,624 |
| Remaining individualsnot grpmax-eligible | 0.0149% | 6,707 |
| European (non-Finnish) | 0.000608% | 164,485 |
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.Pro26=
- Coding
- c.78C>A
- MANE Select
- NM_138961
- Type
- single nucleotide variant
- Location
- chr11:124758520 (GRCh38)
- Gene constraint
- LOEUF 1.009 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.13
- Residue 26
- 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-pro26 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown