BIRC6 p.Arg4605=
c.13813C>A · rs34648875 · VCV791851
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.43%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP 1.9, phastCons 0.98 |
| Overall | ||
| CADD | 7.53 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.43%
African / African-American · 3,323/74,968 alleles
Filtering AF
4.31%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.26%
Overall
0.228%
3,669/1,611,740 alleles · low-frequency
exomes 1,746/1,459,614 · genomes 1,923/152,126 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.43% | 23 |
| Middle Eastern | 0.264% | 378 |
| Remaining individualsnot grpmax-eligible | 0.264% | 378 |
| Admixed American | 0.213% | 468 |
| South Asian | 0.0143% | 7,001 |
| European (non-Finnish) | 0.00203% | 49,146 |
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
- BIRC6
- Protein
- p.Arg4605=
- Coding
- c.13813C>A
- MANE Select
- NM_016252
- dbSNP
- rs34648875
- Type
- single nucleotide variant
- Location
- chr2:32597951 (GRCh38)
- Gene constraint
- LOEUF 0.213 · pLI 1.00 (gnomAD)
- Residue 4605
- the ubc core domain
Similar variants
- BIRC6 p.Gln853Arg Uncertain significance ★★ ⚠ same type
- BIRC6 p.Glu4506Asp Uncertain significance ★★ ⚠ same type
- BIRC6 c.7409-6T>C Likely benign ★★ same type
- BIRC6 p.Ala1549= Benign ★★ same type
- BIRC6 p.Ala3622Val Likely benign ★★ same type
- BIRC6 p.Ala4466= Benign/Likely benign ★★ same type
- BIRC6 p.Asp4607= Benign ★★ same type
- BIRC6 p.Gln1343Leu 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/birc6-p-arg4605 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown