REL p.Tyr56=
c.168T>C · VCV4780797
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00476%, sas)
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 -2 | GERP -1.1 |
| Overall | ||
| CADD | 4.234 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00476%
South Asian · 4/84,042 alleles
Filtering AF
0.00161%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000949%
Overall
0.00142%
22/1,551,526 alleles · very rare
exomes 20/1,399,362 · genomes 2/152,164 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00476% | 21,011 |
| Remaining individualsnot grpmax-eligible | 0.00167% | 59,842 |
| European (non-Finnish) | 0.00149% | 67,031 |
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.Tyr56=
- Coding
- c.168T>C
- MANE Select
- NM_001291746
- Type
- single nucleotide variant
- Location
- chr2:60894411 (GRCh38)
- Gene constraint
- LOEUF 0.416 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 66.46
- Residue 56
- the rhd domain
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-tyr56 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown