AP3B2 p.Arg346=
c.1038C>T · rs1373471918 · VCV1535753
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0257%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.73 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.22 | gain · loss 0.02 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.77 | GERP -1.5, phastCons 1 |
| Overall | ||
| CADD | 20.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0257%
South Asian · 21/81,808 alleles
Filtering AF
0.0171%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0144%
Overall
0.00159%
24/1,511,554 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0257% | 3,896 |
| Middle Eastern | 0.0225% | 4,436 |
| Remaining individualsnot grpmax-eligible | 0.00342% | 29,282 |
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
- AP3B2
- Protein
- p.Arg346=
- Coding
- c.1038C>T
- MANE Select
- NM_001278512
- dbSNP
- rs1373471918
- Type
- single nucleotide variant
- Location
- chr15:82680489 (GRCh38)
- Gene constraint
- LOEUF 0.52 · pLI 0.22 (gnomAD)
- Structure
- AlphaFold pLDDT 75.73
Similar variants
- AP3B2 c.114-1G>A Likely pathogenic ★★ same type
- AP3B2 p.Arg977Ter Pathogenic ★★ same type
- AP3B2 p.Gln839Ter Pathogenic/Likely pathogenic ★★ same type
- AP3B2 c.1110+3G>C Uncertain significance ★★ same type
- AP3B2 c.1853-5C>A Uncertain significance ★★ same type
- AP3B2 c.2834-3C>A Uncertain significance ★★ same type
- AP3B2 p.Ala1076Pro Uncertain significance ★★ same type
- AP3B2 p.Ala1098Asp 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/ap3b2-p-arg346 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown