ELP2 p.Val453=
c.1359A>G · rs148633121 · VCV721087
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0317%, amr)
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 0.34 | GERP -4.8, phastCons 0.68 |
| Overall | ||
| CADD | 6.775 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0317%
Admixed American · 19/59,996 alleles
Filtering AF
0.0207%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0172%
Overall
0.00948%
153/1,614,022 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0317% | 3,158 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,943 |
| European (non-Finnish) | 0.0103% | 9,752 |
| African / African-American | 0.00534% | 18,730 |
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
- ELP2
- Protein
- p.Val453=
- Coding
- c.1359A>G
- MANE Select
- NM_018255
- dbSNP
- rs148633121
- Type
- single nucleotide variant
- Location
- chr18:36156549 (GRCh38)
- Gene constraint
- LOEUF 0.869 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.49 · 4 PDB
- Residue 453
- a β-strand
Similar variants
- ELP2 p.Val453Leu Uncertain significance ★ ⚠ same residue
- ELP2 p.Arg140Ter Pathogenic/Likely pathogenic ★★ same type
- ELP2 p.Arg462Gln Pathogenic/Likely pathogenic ★★ same type
- ELP2 p.Gln192Ter Pathogenic/Likely pathogenic ★★ same type
- ELP2 p.His206Arg Pathogenic/Likely pathogenic ★★ same type
- ELP2 c.523+574G>A Uncertain significance ★★ same type
- ELP2 p.Ala741Val Uncertain significance ★★ ⚠ same type
- ELP2 p.Arg468Trp 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/elp2-p-val453 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown