ELP2 p.Thr646=
c.1938A>G · rs141646549 · VCV781875
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.136%, 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 0.096 | GERP -4.7 |
| Overall | ||
| CADD | 4.423 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.136%
European (non-Finnish) · 1,607/1,179,966 alleles
Filtering AF
0.131%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.128%
Overall
0.11%
1,781/1,614,070 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.136% | 734 |
| Remaining individualsnot grpmax-eligible | 0.134% | 744 |
| Admixed American | 0.117% | 857 |
| African / African-American | 0.024% | 4,169 |
| Middle Eastern | 0.0165% | 6,062 |
| South Asian | 0.0011% | 91,080 |
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.Thr646=
- Coding
- c.1938A>G
- MANE Select
- NM_018255
- dbSNP
- rs141646549
- Type
- single nucleotide variant
- Location
- chr18:36164651 (GRCh38)
- Gene constraint
- LOEUF 0.869 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.49 · 4 PDB
Similar variants
- 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
- ELP2 p.Asp71Gly 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-thr646 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown