REL p.Ala442=
c.1326G>A · rs372798591 · VCV2056600
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0495%, mid)
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 -2.6 | GERP -2.3 |
| Overall | ||
| CADD | 2.788 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0495%
Middle Eastern · 3/6,058 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00718%
Overall
0.00341%
55/1,614,078 alleles · ultra-rare
exomes 47/1,461,788 · genomes 8/152,290 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0495% | 2,019 |
| African / African-American | 0.012% | 8,337 |
| Admixed American | 0.00833% | 12,004 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,255 |
| European (non-Finnish) | 0.0028% | 35,757 |
| South Asian | 0.0022% | 45,537 |
| Finnishnot grpmax-eligible | 0.00156% | 63,994 |
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.Ala442=
- Coding
- c.1326G>A
- MANE Select
- NM_001291746
- dbSNP
- rs372798591
- Type
- single nucleotide variant
- Location
- chr2:60922097 (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-ala442 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown