ATF6 p.Leu46=
c.136T>C · rs151136116 · VCV1134397
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0494%, 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 -1.7 | GERP 1.2 |
| Overall | ||
| CADD | 3.904 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0494%
Middle Eastern · 3/6,078 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00716%
Overall
0.00304%
49/1,613,470 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0494% | 2,026 |
| South Asian | 0.00769% | 13,010 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,819 |
| African / African-American | 0.004% | 24,976 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,596 |
| European (non-Finnish) | 0.00271% | 36,863 |
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
- ATF6
- Protein
- p.Leu46=
- Coding
- c.136T>C
- MANE Select
- NM_007348
- dbSNP
- rs151136116
- Type
- single nucleotide variant
- Location
- chr1:161778297 (GRCh38)
- Gene constraint
- LOEUF 0.882 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 56.09
- Residue 46
- the 'transcription activation' region
Similar variants
- ATF6 p.Leu46Ser Uncertain significance ★★ ⚠ same residue
- ATF6 c.1533+1G>C Pathogenic ★★ same type
- ATF6 c.160-1G>A Likely pathogenic ★★ same type
- ATF6 c.484+1G>A Likely pathogenic ★★ same type
- ATF6 c.484+1G>T Likely pathogenic ★★ same type
- ATF6 c.82+5G>T Pathogenic ★★ same type
- ATF6 p.Arg324Cys Pathogenic ★★ same type
- ATF6 p.Arg376Ter Pathogenic ★★ 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/atf6-p-leu46 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown