ITM2B p.Ala259=
c.777C>T · rs146553069 · VCV1595711
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0581%, eas)
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 -5.3 | GERP -4.9 |
| Overall | ||
| CADD | 8.52 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0581%
East Asian · 26/44,774 alleles
Filtering AF
0.0406%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0348%
Overall
0.00397%
64/1,611,492 alleles · ultra-rare
exomes 56/1,459,442 · genomes 8/152,050 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0581% | 1,722 |
| South Asian | 0.0165% | 6,059 |
| African / African-American | 0.00802% | 12,465 |
| Remaining individualsnot grpmax-eligible | 0.00802% | 12,476 |
| Admixed American | 0.00167% | 59,934 |
| European (non-Finnish) | 0.000934% | 107,115 |
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.Ala259=
- Coding
- c.777C>T
- MANE Select
- NM_021999
- dbSNP
- rs146553069
- Type
- single nucleotide variant
- Location
- chr13:48261200 (GRCh38)
- Gene constraint
- LOEUF 0.734 · pLI 0.58 (gnomAD)
- Structure
- AlphaFold pLDDT 76.31 · 2 PDB
Similar variants
- 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
- ITM2B p.His200Asp 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-ala259 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown