ESPNL p.Ala483=
c.1449G>A · rs368696053 · VCV2652059
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0996%, mid)
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 -7.7 | GERP -3.8 |
| Overall | ||
| CADD | 0.532 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0996%
Middle Eastern · 6/6,022 alleles
Filtering AF
0.0433%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0296%
Overall
0.0172%
277/1,612,790 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0996% | 1,004 |
| Remaining individualsnot grpmax-eligible | 0.0256% | 3,904 |
| European (non-Finnish) | 0.0187% | 5,339 |
| Admixed American | 0.0167% | 6,001 |
| South Asian | 0.0165% | 6,070 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0101% | 9,867 |
| African / African-American | 0.004% | 25,019 |
| Finnishnot grpmax-eligible | 0.00318% | 31,479 |
| East Asian | 0.00223% | 44,876 |
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
- ESPNL
- Protein
- p.Ala483=
- Coding
- c.1449G>A
- MANE Select
- NM_194312
- dbSNP
- rs368696053
- Type
- single nucleotide variant
- Location
- chr2:238130163 (GRCh38)
- Gene constraint
- LOEUF 1.651 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.57
- Residue 483
- the 'disordered' region
Similar variants
- ESPNL p.Arg167Gln Benign ★★ same type
- ESPNL p.Arg351Cys Benign ★★ ⚠ same type
- ESPNL c.672+1G>A Uncertain significance ★ same type
- ESPNL p.Ala112Ser Uncertain significance ★ ⚠ same type
- ESPNL p.Ala144Asp Uncertain significance ★ ⚠ same type
- ESPNL p.Ala144Thr Uncertain significance ★ ⚠ same type
- ESPNL p.Ala145Thr Uncertain significance ★ ⚠ same type
- ESPNL p.Ala159Thr 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/espnl-p-ala483 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown