APAF1 p.Gln190Pro
c.569A>C · VCV3878024
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.3747 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| AlphaMissense | 0.3747 | ambiguous |
|---|---|---|
| REVEL | 0.624 | indeterminate |
| SaProt | LLR -8.62 | tolerated |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 0.87 | unconstrained · MANE · 84 kb · p 8.3e-07 · regional, not allelic |
| Overall | ||
| CADD | 25.4 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- APAF1
- Protein
- p.Gln190Pro
- Coding
- c.569A>C
- MANE Select
- NM_181861
- Type
- single nucleotide variant
- Location
- chr12:98659202 (GRCh38)
- Gene constraint
- LOEUF 0.664 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.60 · 14 PDB
- Residue 190
- the nb-arc domain
Similar variants
- APAF1 c.2047-3T>C Benign ★★ same type
- APAF1 p.Glu625Ala Benign ★★ same type
- APAF1 p.Ser871Leu Likely benign ★★ ⚠ same type
- APAF1 p.Thr446Ser Benign ★★ same type
- APAF1 p.Tyr359= Benign ★★ same type
- APAF1 p.Ala1025Val Uncertain significance ★ ⚠ same type
- APAF1 p.Ala223Ser Uncertain significance ★ ⚠ same type
- APAF1 p.Ala304Thr 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/apaf1-p-gln190pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown