RAP1A p.Val46=
c.138C>T · rs377603275 · VCV761251
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0264%, sas)
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 1.6 | GERP -0.36, phastCons 1 |
| Overall | ||
| CADD | 10.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0264%
South Asian · 24/90,906 alleles
Filtering AF
0.0181%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0154%
Overall
0.00292%
47/1,609,566 alleles · ultra-rare
exomes 31/1,459,934 · genomes 16/149,632 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0264% | 3,788 |
| African / African-American | 0.0258% | 3,881 |
| Middle Eastern | 0.0165% | 6,072 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,334 |
| European (non-Finnish) | 0.00017% | 589,379 |
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
- RAP1A
- Protein
- p.Val46=
- Coding
- c.138C>T
- MANE Select
- NM_002884
- dbSNP
- rs377603275
- Type
- single nucleotide variant
- Location
- chr1:111697452 (GRCh38)
- Gene constraint
- LOEUF 0.433 · pLI 0.99 (gnomAD)
- Structure
- AlphaFold pLDDT 92.17 · 4 PDB
- Residue 46
- a β-strand
Similar variants
- RAP1A c.126+185A>G Benign ★★ same type
- RAP1A c.57+176C>T Benign ★★ same type
- RAP1A c.57+29T>A Benign ★★ same type
- RAP1A c.57+45G>T Benign ★★ same type
- RAP1A c.58-48A>T Benign ★★ same type
- RAP1A c.*29+16C>T Benign ★★ same type
- RAP1A c.*29+97C>G Benign ★★ same type
- RAP1A p.Ala142= Likely benign ★★ 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/rap1a-p-val46 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown