APBA1 p.Ile456=
c.1368C>T · rs745501677 · VCV2659244
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00381%, nfe)
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 -2.8 | GERP -3.3 |
| Overall | ||
| CADD | 6.121 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00381%
European (non-Finnish) · 45/1,180,030 alleles
Filtering AF
0.00291%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0026%
Overall
0.0031%
50/1,614,020 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00381% | 26,223 |
| Admixed American | 0.00333% | 29,994 |
| East Asian | 0.00223% | 44,880 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
| South Asian | 0.0011% | 91,084 |
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
- APBA1
- Protein
- p.Ile456=
- Coding
- c.1368C>T
- MANE Select
- NM_001163
- dbSNP
- rs745501677
- Type
- single nucleotide variant
- Location
- chr9:69467937 (GRCh38)
- Gene constraint
- LOEUF 0.978 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 58.85 · 8 PDB
- Residue 456
- a turn
Similar variants
- APBA1 p.Asn810Ser Uncertain significance ★★ ⚠ same type
- APBA1 p.Ala225Val Uncertain significance ★ ⚠ same type
- APBA1 p.Ala329Val Uncertain significance ★ ⚠ same type
- APBA1 p.Ala345Thr Uncertain significance ★ ⚠ same type
- APBA1 p.Ala506Pro Uncertain significance ★ ⚠ same type
- APBA1 p.Ala574Val Uncertain significance ★ ⚠ same type
- APBA1 p.Arg143Cys Uncertain significance ★ ⚠ same type
- APBA1 p.Arg177His 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/apba1-p-ile456 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown