ESAM p.Pro181=
c.543C>T · rs139265422 · VCV2642498
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.647%, 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 -3 | GERP -2.5 |
| Overall | ||
| CADD | 0.365 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.647%
European (non-Finnish) · 7,633/1,180,032 alleles
Filtering AF
0.635%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.63%
Overall
0.519%
8,378/1,614,154 alleles · rare
exomes 7,858/1,461,798 · genomes 520/152,356 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.647% | 155 |
| Remaining individualsnot grpmax-eligible | 0.506% | 198 |
| South Asian | 0.25% | 399 |
| Finnishnot grpmax-eligible | 0.125% | 800 |
| African / African-American | 0.0973% | 1,028 |
| Admixed American | 0.0683% | 1,464 |
| Middle Eastern | 0.0165% | 6,052 |
| East Asian | 0.00891% | 11,220 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,803 |
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.Pro181=
- Coding
- c.543C>T
- MANE Select
- NM_138961
- dbSNP
- rs139265422
- Type
- single nucleotide variant
- Location
- chr11:124756271 (GRCh38)
- Gene constraint
- LOEUF 1.009 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.13
- Residue 181
- a UniProt-annotated variant site (in nedihss); the ig-like c2-type domain
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 c.451+1G>A Likely pathogenic ★ same type
- ESAM c.608-1G>A Likely pathogenic ★ same type
- ESAM c.70+1G>T 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-pro181 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown