ITM2B p.Ala110=
c.330T>C · VCV4919994
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00136%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.024 | GERP -1.3, phastCons 0.91 |
| Overall | ||
| CADD | 8.144 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00136%
European (non-Finnish) · 16/1,179,278 alleles
Filtering AF
0.000803%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00065%
Overall
0.000992%
16/1,613,326 alleles · very rare
exomes 16/1,461,026 · genomes 0/152,300 · joint denominator
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
- ITM2B
- Protein
- p.Ala110=
- Coding
- c.330T>C
- MANE Select
- NM_021999
- Type
- single nucleotide variant
- Location
- chr13:48256260 (GRCh38)
- Gene constraint
- LOEUF 0.734 · pLI 0.58 (gnomAD)
- Structure
- AlphaFold pLDDT 76.31 · 2 PDB
- Residue 110
- the 'necessary for interaction with app and inhibitor effects on app processing' region
Similar variants
- ITM2B p.Ala110Ser Uncertain significance ★ ⚠ same residue
- ITM2B p.Ter267Leu Likely pathogenic ★★ same type
- ITM2B p.Ala62Val Uncertain significance ★★ ⚠ same type
- ITM2B p.Arg221Gln Uncertain significance ★★ ⚠ same type
- ITM2B p.Arg233Cys Uncertain significance ★★ ⚠ same type
- ITM2B p.Asp85Asn Uncertain significance ★★ ⚠ same type
- ITM2B p.Glu126Val Uncertain significance ★★ ⚠ same type
- ITM2B p.Glu19Lys 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/itm2b-p-ala110 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown