RGR p.Ala99=
c.297G>A · rs373030585 · VCV1109360
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.024%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.045 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -13 |
| Overall | ||
| CADD | 0.005 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.024%
African / African-American · 18/74,926 alleles
Filtering AF
0.0155%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0128%
Overall
0.00223%
36/1,614,022 alleles · ultra-rare
exomes 24/1,461,816 · genomes 12/152,206 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.024% | 4,163 |
| Middle Eastern | 0.0164% | 6,082 |
| East Asian | 0.00446% | 22,444 |
| Admixed American | 0.00333% | 29,999 |
| South Asian | 0.00329% | 30,362 |
| Finnishnot grpmax-eligible | 0.00312% | 32,018 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,480 |
| European (non-Finnish) | 0.000593% | 168,573 |
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
- RGR
- Protein
- p.Ala99=
- Coding
- c.297G>A
- MANE Select
- NM_001012720
- dbSNP
- rs373030585
- Type
- single nucleotide variant
- Location
- chr10:84248982 (GRCh38)
- Structure
- AlphaFold pLDDT 62.88
Similar variants
- RGR p.Ala99Val Uncertain significance ★ ⚠ same residue
- RGR c.358+1G>A Uncertain significance ★★ same type
- RGR p.Ala110Thr Uncertain significance ★★ ⚠ same type
- RGR p.Ala186Thr Uncertain significance ★★ ⚠ same type
- RGR p.Ala217Gly Uncertain significance ★★ ⚠ same type
- RGR p.Ala234Thr Uncertain significance ★★ ⚠ same type
- RGR p.Ala251Thr Uncertain significance ★★ ⚠ same type
- RGR p.Ala251Val 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/rgr-p-ala99 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown