BIRC6 p.Leu3989=
c.11967C>T · rs150058017 · VCV2650817
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.215%, 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 -2.4 | GERP -3.7 |
| Overall | ||
| CADD | 4.838 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.215%
Middle Eastern · 13/6,056 alleles
Filtering AF
0.127%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.101%
Overall
0.0133%
215/1,613,388 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.215% | 466 |
| Ashkenazi Jewishnot grpmax-eligible | 0.142% | 705 |
| Admixed American | 0.0501% | 1,997 |
| Remaining individualsnot grpmax-eligible | 0.0336% | 2,974 |
| European (non-Finnish) | 0.00916% | 10,923 |
| African / African-American | 0.00133% | 75,000 |
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.Leu3989=
- Coding
- c.11967C>T
- MANE Select
- NM_016252
- dbSNP
- rs150058017
- Type
- single nucleotide variant
- Location
- chr2:32529697 (GRCh38)
- Gene constraint
- LOEUF 0.213 · pLI 1.00 (gnomAD)
- Residue 3989
- an α-helix; the ubiquitin-like 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.Arg4605= Benign ★★ same type
- BIRC6 p.Asp4607= 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-leu3989 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown