ABI2 p.Pro375Ala
c.1123C>G · VCV3993301
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0291%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.145 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2.1, phastCons 1 |
| Regional constraint | o/e 0.94 | unconstrained · MANE · 37 kb · p 0.22 · regional, not allelic |
| Overall | ||
| CADD | 25.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0291%
Admixed American · 17/58,496 alleles
Filtering AF
0.0184%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0152%
Overall
0.00106%
17/1,606,560 alleles · ultra-rare
exomes 17/1,454,238 · genomes 0/152,322 · 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
- ABI2
- Protein
- p.Pro375Ala
- Coding
- c.1123C>G
- MANE Select
- NM_001375670
- Type
- single nucleotide variant
- Location
- chr2:203402665 (GRCh38)
- Gene constraint
- LOEUF 0.585 · pLI 0.45 (gnomAD)
- Structure
- AlphaFold pLDDT 67.14 · 6 PDB
- Residue 375
- a UniProt-annotated variant site (found in a consanguineous family with autosomal recessive intellectual disability; likely pathogenic); the 'disordered' region
Similar variants
- ABI2 p.Ala128Ser Uncertain significance ★ same type
- ABI2 p.Arg219His Uncertain significance ★ same type
- ABI2 p.Arg239Gly Uncertain significance ★ same type
- ABI2 p.Arg255Trp Uncertain significance ★ same type
- ABI2 p.Arg84Gln Uncertain significance ★ same type
- ABI2 p.Asn115Ser Uncertain significance ★ same type
- ABI2 p.Asn385Lys Uncertain significance ★ same type
- ABI2 p.Asn426His 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/abi2-p-pro375ala (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown