REL p.Leu319=
c.957C>T · VCV3670171
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0281%, afr)
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 -0.13 | GERP -2.5 |
| Overall | ||
| CADD | 6.84 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0281%
African / African-American · 21/74,632 alleles
Filtering AF
0.0188%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0158%
Overall
0.00299%
48/1,604,852 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0281% | 3,554 |
| Middle Eastern | 0.0216% | 4,638 |
| South Asian | 0.00661% | 15,120 |
| European (non-Finnish) | 0.00162% | 61,773 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,094 |
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.Leu319=
- Coding
- c.957C>T
- MANE Select
- NM_001291746
- Type
- single nucleotide variant
- Location
- chr2:60920608 (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-leu319 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown