APAF1 p.Lys916=
c.2748G>A · rs755943177 · VCV3042337
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00602%, nfe)
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 3.9 | GERP 0.015, phastCons 1 |
| Overall | ||
| CADD | 8.342 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00602%
European (non-Finnish) · 71/1,179,650 alleles
Filtering AF
0.00486%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00447%
Overall
0.00459%
74/1,613,372 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00602% | 16,615 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,223 |
| South Asian | 0.0011% | 91,076 |
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.Lys916=
- Coding
- c.2748G>A
- MANE Select
- NM_181861
- dbSNP
- rs755943177
- Type
- single nucleotide variant
- Location
- chr12:98708611 (GRCh38)
- Gene constraint
- LOEUF 0.664 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.60 · 14 PDB
- Residue 916
- the 'interpropeller linker' region
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.Gln416= Likely benign same condition
- APAF1 p.Ile1038Val 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-lys916 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown