RARA p.Pro279=
c.837C>T · rs77633370 · VCV780426
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.21%, 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 -6.4 | GERP -3.7 |
| Overall | ||
| CADD | 10.92 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.21%
African / African-American · 2,406/75,020 alleles
Filtering AF
3.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.06%
Overall
0.467%
7,540/1,614,144 alleles · low-frequency
exomes 5,833/1,461,880 · genomes 1,707/152,264 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.21% | 31 |
| Amishnot grpmax-eligible | 3.07% | 33 |
| Remaining individualsnot grpmax-eligible | 0.515% | 194 |
| European (non-Finnish) | 0.376% | 266 |
| Admixed American | 0.285% | 351 |
| Middle Eastern | 0.231% | 433 |
| Ashkenazi Jewishnot grpmax-eligible | 0.209% | 478 |
| South Asian | 0.0856% | 1,168 |
| Finnishnot grpmax-eligible | 0.0344% | 2,911 |
| East Asian | 0.00223% | 44,876 |
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
- RARA
- Protein
- p.Pro279=
- Coding
- c.837C>T
- MANE Select
- NM_000964
- dbSNP
- rs77633370
- Type
- single nucleotide variant
- Location
- chr17:40354331 (GRCh38)
- Gene constraint
- LOEUF 0.254 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 79.49 · 14 PDB
- Residue 279
- the nr lbd domain; a turn
Similar variants
- RARA p.Ala104Thr Uncertain significance ★ ⚠ same type
- RARA p.Ala438Val Uncertain significance ★ ⚠ same type
- RARA p.Arg162Gln Uncertain significance ★ ⚠ same type
- RARA p.Arg276Gln Conflicting classifications of pathogenicity ★ ⚠ same type
- RARA p.Arg276Trp Uncertain significance ★ ⚠ same type
- RARA p.Arg347Leu Uncertain significance ★ ⚠ same type
- RARA p.Arg370Cys Uncertain significance ★ ⚠ same type
- RARA p.Arg394Gln 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/rara-p-pro279 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown