APAF1 p.Gln416=
c.1248G>A · rs147249307 · VCV3042926
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.193%, afr)
Conditions
1
APAF1-related disorder
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 0.33 | GERP -4.2, phastCons 0.94 |
| Overall | ||
| CADD | 3.824 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.193%
African / African-American · 145/75,012 alleles
Filtering AF
0.168%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.158%
Overall
0.0128%
206/1,613,960 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.193% | 517 |
| Admixed American | 0.0516% | 1,936 |
| Remaining individualsnot grpmax-eligible | 0.0384% | 2,604 |
| South Asian | 0.0022% | 45,539 |
| European (non-Finnish) | 0.000339% | 294,972 |
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
- APAF1
- Protein
- p.Gln416=
- Coding
- c.1248G>A
- MANE Select
- NM_181861
- dbSNP
- rs147249307
- Type
- single nucleotide variant
- Location
- chr12:98666243 (GRCh38)
- Gene constraint
- LOEUF 0.664 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.60 · 14 PDB
- Residue 416
- an α-helix
Disease context
APAF1-related disorder
Similar variants
- APAF1 c.3457-7T>C Likely benign same condition
- APAF1 c.527-10C>T Likely benign same condition
- APAF1 c.956-4A>T Likely benign same condition
- APAF1 c.*3T>C Benign same condition
- APAF1 p.Ala304= Likely benign same condition
- APAF1 p.Ala984= Benign same condition
- APAF1 p.Ile1038Val Benign same condition
- APAF1 p.Ile821= Likely benign same condition
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-gln416 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown