CERT1 p.Ala449=
c.1347A>G · VCV4970770
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000256%, 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 0.009 | GERP -2.6, phastCons 0.96 |
| Overall | ||
| CADD | 10.62 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000256%
European (non-Finnish) · 3/1,171,942 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000207%
3/1,445,966 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
- CERT1
- Protein
- p.Ala449=
- Coding
- c.1347A>G
- MANE Select
- NM_001379029
- Type
- single nucleotide variant
- Location
- chr5:75385972 (GRCh38)
- Gene constraint
- LOEUF 0.656 · pLI 0.10 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.75 · 27 PDB
- Residue 449
- the start domain; a β-strand
Similar variants
- CERT1 p.Ala449Val Uncertain significance ★ ⚠ same residue
- CERT1 p.Ser135Phe Likely pathogenic ★★ same type
- CERT1 p.Thr166Ala Pathogenic/Likely pathogenic ★★ ⚠ same type
- CERT1 c.-195C>T Uncertain significance ★★ same type
- CERT1 p.Ala538Val Uncertain significance ★★ ⚠ same type
- CERT1 p.Asp80Asn Uncertain significance ★★ ⚠ same type
- CERT1 p.Cys185Phe Uncertain significance ★★ ⚠ same type
- CERT1 p.Gly452Asp Uncertain significance ★★ ⚠ 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/cert1-p-ala449 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown