Is AIP c.645+5T>C pathogenic?

AIP c.645+5T>C is classified Uncertain significance in AIP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-22). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with AIP c.645+5T>C?

AIP c.645+5T>C is associated with hereditary neoplastic syndrome (ClinVar).

How common is AIP c.645+5T>C in the general population?

AIP c.645+5T>C is absent from gnomAD v4.1 (gnomAD).

AIP c.645+5T>C

rs2495406065 · VCV3223624

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +5	donor splice region (+5, 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 -4.7	GERP -2.6
Overall
CADD	1.452	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AIP
Coding: c.645+5T>C
MANE Select: NM_017900 · reported on NM_003977
dbSNP: rs2495406065
Type: single nucleotide variant
Location: chr11:67490219 (GRCh38)
Structure: AlphaFold pLDDT 70.14 · 81 PDB

Full AIP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-645-plus-5t-c (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown