APAF1 p.Arg812=
c.2436G>A · rs777352704 · VCV744827
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00667%, afr)
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 -0.26 | GERP -4.1 |
| Overall | ||
| CADD | 3.566 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00667%
African / African-American · 5/74,944 alleles
Filtering AF
0.00255%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00161%
Overall
0.00062%
10/1,614,040 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00667% | 14,989 |
| European (non-Finnish) | 0.000424% | 236,004 |
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.Arg812=
- Coding
- c.2436G>A
- MANE Select
- NM_181861
- dbSNP
- rs777352704
- Type
- single nucleotide variant
- Location
- chr12:98699539 (GRCh38)
- Gene constraint
- LOEUF 0.664 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.60 · 14 PDB
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-arg812 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown