ERLIN2 p.Ser43=
c.129G>A · rs376188007 · VCV700535
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
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 -2.1 | GERP -3.1 |
| Overall | ||
| CADD | 7.085 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,054 alleles
Filtering AF
0.00723%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0055%
Overall
0.00167%
27/1,612,566 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,054 |
| East Asian | 0.0134% | 7,459 |
| African / African-American | 0.0134% | 7,491 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,803 |
| Admixed American | 0.00167% | 59,944 |
| European (non-Finnish) | 0.000509% | 196,528 |
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.Ser43=
- Coding
- c.129G>A
- MANE Select
- NM_007175
- dbSNP
- rs376188007
- Type
- single nucleotide variant
- Location
- chr8:37740386 (GRCh38)
- Gene constraint
- LOEUF 0.703 · pLI 0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.35 · 5 PDB
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-ser43 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown