BIRC6 p.Leu4174=
c.12522A>C · rs146143546 · VCV740578
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0419%, nfe)
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 -0.54 | GERP -5.5 |
| Overall | ||
| CADD | 2.069 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0419%
European (non-Finnish) · 494/1,179,886 alleles
Filtering AF
0.0388%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0376%
Overall
0.0327%
527/1,614,030 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0419% | 2,388 |
| Remaining individualsnot grpmax-eligible | 0.0352% | 2,840 |
| African / African-American | 0.00933% | 10,724 |
| Admixed American | 0.00333% | 30,011 |
| Finnishnot grpmax-eligible | 0.00312% | 32,012 |
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.Leu4174=
- Coding
- c.12522A>C
- MANE Select
- NM_016252
- dbSNP
- rs146143546
- Type
- single nucleotide variant
- Location
- chr2:32543471 (GRCh38)
- Gene constraint
- LOEUF 0.213 · pLI 1.00 (gnomAD)
- Residue 4174
- an α-helix
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-leu4174 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown