REL p.Asp435=
c.1305T>C · rs113097160 · VCV2084155
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.537%, 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 -0.049 | GERP -2.6, phastCons 0.9 |
| Overall | ||
| CADD | 2.812 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.537%
African / African-American · 403/75,064 alleles
Filtering AF
0.494%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.477%
Overall
0.0288%
465/1,614,208 alleles · rare
exomes 255/1,461,846 · genomes 210/152,362 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.537% | 186 |
| Remaining individualsnot grpmax-eligible | 0.0736% | 1,359 |
| Middle Eastern | 0.033% | 3,030 |
| Admixed American | 0.0183% | 5,457 |
| South Asian | 0.0022% | 45,544 |
| European (non-Finnish) | 8.47e-05% | 1,180,012 |
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.Asp435=
- Coding
- c.1305T>C
- MANE Select
- NM_001291746
- dbSNP
- rs113097160
- Type
- single nucleotide variant
- Location
- chr2:60922076 (GRCh38)
- Gene constraint
- LOEUF 0.416 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 66.46
- Residue 435
- the 'disordered' region
Similar variants
- REL p.Asp435Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
- 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
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-asp435 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown