EN1 p.Ala61=
c.183G>A · rs764736993 · VCV3025567
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0663%, 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 0.19 | GERP -1.6, phastCons 0.94 |
| Overall | ||
| CADD | 11.63 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0663%
European (non-Finnish) · 705/1,063,848 alleles
Filtering AF
0.0622%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0605%
Overall
0.055%
746/1,355,836 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0663% | 1,509 |
| Remaining individualsnot grpmax-eligible | 0.0446% | 2,242 |
| Admixed American | 0.0354% | 2,827 |
| Middle Eastern | 0.027% | 3,700 |
| African / African-American | 0.0123% | 8,109 |
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
- EN1
- Protein
- p.Ala61=
- Coding
- c.183G>A
- MANE Select
- NM_001426
- dbSNP
- rs764736993
- Type
- single nucleotide variant
- Location
- chr2:118846985 (GRCh38)
- Gene constraint
- LOEUF 0.724 · pLI 0.52 (gnomAD)
- Structure
- AlphaFold pLDDT 58.76
- Residue 61
- the 'disordered' region
Similar variants
- EN1 p.Ala61Thr Uncertain significance ★ ⚠ same residue
- EN1 p.Ala201= Likely benign ★★ same type
- EN1 p.Pro76= Likely benign ★★ same type
- EN1 p.Ala132Thr Uncertain significance ★ ⚠ same type
- EN1 p.Ala150Val Uncertain significance ★ ⚠ same type
- EN1 p.Ala151Ser Uncertain significance ★ ⚠ same type
- EN1 p.Ala15Pro Uncertain significance ★ ⚠ same type
- EN1 p.Ala190Val Uncertain significance ★ ⚠ 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/en1-p-ala61 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown