AIP c.99+4C>T
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
Conditions
1
hereditary neoplastic syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +4 | donor splice region (+4, within the first 6 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.71 | GERP -3.5, phastCons 0.004 |
| Non-coding constraint | Z -0.48 | 1 kb window · o/e 1.04 · regional · uncalibrated |
| Overall | ||
| CADD | 13.03 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,179,506 alleles
Overall
6.84e-05%
1/1,461,252 alleles · very rare
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
- AIP
- Coding
- c.99+4C>T
- MANE Select
- NM_003977
- dbSNP
- rs2134247837
- Type
- single nucleotide variant
- Location
- chr11:67483261 (GRCh38)
- Gene constraint
- LOEUF 0.626 · pLI 0.28 (gnomAD)
- Structure
- AlphaFold pLDDT 91.09 · 5 PDB
Similar variants
- AIP p.Arg271Trp Pathogenic/Likely pathogenic ★★ same condition
- AIP p.Arg304Ter Pathogenic ★★ same condition
- AIP p.Arg81Ter Pathogenic ★★ same condition
- AIP p.Cys238Tyr Likely pathogenic ★★ same condition
- AIP p.Gln126Ter Pathogenic ★★ same condition
- AIP p.Gln14Ter Pathogenic ★★ same condition
- AIP p.Gln217Ter Pathogenic ★★ same condition
- AIP p.Trp168Ter Pathogenic ★★ same condition
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/aip-c-99-plus-4c-t (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown