APAF1 p.Tyr359=
c.1077T>C · rs57171247 · VCV773029
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 8.63%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>G here scores Δ0.55 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.2 | GERP -3.3 |
| Overall | ||
| CADD | 3.48 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.63%
African / African-American · 6,472/74,986 alleles
Filtering AF
8.46%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 8.38%
Overall
0.454%
7,329/1,613,998 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 8.63% | 12 |
| Admixed American | 0.522% | 192 |
| Remaining individualsnot grpmax-eligible | 0.517% | 194 |
| Middle Eastern | 0.313% | 319 |
| South Asian | 0.0307% | 3,253 |
| European (non-Finnish) | 0.0147% | 6,781 |
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.Tyr359=
- Coding
- c.1077T>C
- MANE Select
- NM_181861
- dbSNP
- rs57171247
- Type
- single nucleotide variant
- Location
- chr12:98665674 (GRCh38)
- Gene constraint
- LOEUF 0.664 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.60 · 14 PDB
- Residue 359
- 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.Ala1025Val Uncertain significance ★ ⚠ same type
- APAF1 p.Ala223Ser Uncertain significance ★ ⚠ same type
- APAF1 p.Ala304Thr Uncertain significance ★ ⚠ same type
- APAF1 p.Ala584Asp 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-tyr359 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown