ERLIN2 p.Leu283=
c.849G>C · rs1269375247 · VCV2998566
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000254%, nfe)
Conditions
1
Spastic paraplegia
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 5.2 | GERP -1.7, phastCons 1 |
| Overall | ||
| CADD | 6.942 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000254%
European (non-Finnish) · 3/1,179,678 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000205%
3/1,461,564 alleles · very rare
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
- ERLIN2
- Protein
- p.Leu283=
- Coding
- c.849G>C
- MANE Select
- NM_007175
- dbSNP
- rs1269375247
- Type
- single nucleotide variant
- Location
- chr8:37753944 (GRCh38)
- Gene constraint
- LOEUF 0.703 · pLI 0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.35 · 5 PDB
- Residue 283
- the 'interaction with erlin1' region
Similar variants
- ERLIN2 p.Ala151Val Pathogenic/Likely pathogenic ★★ same condition
- ERLIN2 c.298+5G>A Uncertain significance ★★ same condition
- ERLIN2 c.819+3A>G Uncertain significance ★★ same condition
- ERLIN2 p.Ala290Val Uncertain significance ★★ ⚠ same condition
- ERLIN2 p.Ala99Thr Uncertain significance ★★ ⚠ same condition
- ERLIN2 p.Asn93Asp Uncertain significance ★★ ⚠ same condition
- ERLIN2 p.Gln154Pro Uncertain significance ★★ ⚠ same condition
- ERLIN2 p.Gln63Arg Uncertain significance ★★ ⚠ same condition
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/erlin2-p-leu283 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown