Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.3%, 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 -0.5 | GERP -1.9 |
| Overall | ||
| CADD | 5.288 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.3%
African / African-American · 1,724/75,040 alleles
Filtering AF
2.21%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.17%
Overall
0.128%
2,066/1,614,180 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.3% | 44 |
| Admixed American | 0.23% | 435 |
| Remaining individualsnot grpmax-eligible | 0.165% | 607 |
| Middle Eastern | 0.0825% | 1,212 |
| South Asian | 0.00878% | 11,386 |
| European (non-Finnish) | 0.00746% | 13,409 |
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
- CHAF1A
- Protein
- p.Ala70=
- Coding
- c.210C>G
- MANE Select
- NM_005483
- dbSNP
- rs2230633
- Type
- single nucleotide variant
- Location
- chr19:4409009 (GRCh38)
- Gene constraint
- LOEUF 0.109 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 59.06 · 11 PDB
- Residue 70
- the 'binds to cbx1 chromo shadow domain' region
Similar variants
- CHAF1A p.Ala70Val Uncertain significance ★ ⚠ same residue
- CHAF1A p.Ala70Thr Likely benign ★ same residue
- UBXN6 p.Arg313Leu Uncertain significance ★★ ⚠ same type
- CHAF1A p.Trp668Ter Pathogenic ★ same type
- CHAF1A p.Ala140Gly Uncertain significance ★ ⚠ same type
- CHAF1A p.Ala16Pro Uncertain significance ★ ⚠ same type
- CHAF1A p.Ala193Ser Uncertain significance ★ ⚠ same type
- CHAF1A p.Ala193Thr 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/chaf1a-p-ala70 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown