ATF6 p.Ala33=
c.99T>C · rs2525108462 · VCV1922769
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>A here scores Δ0.54 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.43 | GERP 3.8, phastCons 1 |
| Overall | ||
| CADD | 10.55 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,179,758 alleles
Overall
6.84e-05%
1/1,461,286 alleles · very rare
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.Ala33=
- Coding
- c.99T>C
- MANE Select
- NM_007348
- dbSNP
- rs2525108462
- Type
- single nucleotide variant
- Location
- chr1:161778260 (GRCh38)
- Gene constraint
- LOEUF 0.882 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 56.09
- Residue 33
- the 'transcription activation' region
Similar variants
- 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
- ATF6 p.Gln237Ter 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-ala33 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown