REL p.Ser491=
c.1473A>G · rs767394966 · VCV2786425
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000678%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.7 | GERP -2.6 |
| Overall | ||
| CADD | 4.801 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000678%
European (non-Finnish) · 8/1,180,022 alleles
Filtering AF
0.000292%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000211%
Overall
0.000496%
8/1,614,060 alleles · very rare
exomes 7/1,461,870 · genomes 1/152,190 · joint denominator
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
- REL
- Protein
- p.Ser491=
- Coding
- c.1473A>G
- MANE Select
- NM_001291746
- dbSNP
- rs767394966
- Type
- single nucleotide variant
- Location
- chr2:60922244 (GRCh38)
- Gene constraint
- LOEUF 0.416 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 66.46
Similar variants
- REL p.Asp224Asn Uncertain significance ★★ ⚠ same type
- REL p.Gln503His Uncertain significance ★★ ⚠ same type
- REL p.Leu298Val Uncertain significance ★★ ⚠ same type
- REL p.Met372Lys Uncertain significance ★★ ⚠ same type
- REL p.Met372Val Uncertain significance ★★ ⚠ same type
- REL p.Phe559Leu Uncertain significance ★★ ⚠ same type
- REL p.Ser556Gly Uncertain significance ★★ ⚠ same type
- REL p.Ser563Asn 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/rel-p-ser491 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown