ACE2 c.2309+2T>A
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
Consequence
canonical splice-site (±1/±2)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | canonical splice-site (±1/±2) | predicted loss-of-function |
|---|---|---|
| Splicing | ||
| Splice region | donor +2 | canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone |
| SpliceAI | Δ1.00 | donor loss · deltas |
| Pangolin | Δ0.87 | loss · gain 0.01 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 9.3 | GERP 1.8, phastCons 1 |
| Non-coding constraint | — | not assessed · autosomes only, so chrX has no window · absence ≠ unconstrained |
| Overall | ||
| CADD | 24.7 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
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
- ACE2
- Coding
- c.2309+2T>A
- MANE Select
- NM_001371415
- Type
- single nucleotide variant
- Location
- chrX:15564022 (GRCh38)
- Structure
- AlphaFold pLDDT 91.13 · 328 PDB
Similar variants
- ACE2 c.584-7C>A Likely benign ★★ same type
- ACE2 p.Asn690= Benign ★★ same type
- ACE2 p.Lys26Arg Likely benign ★★ same type
- BMX p.Ala214Val Benign ★★ ⚠ same type
- ACE2 p.Arg161Lys Uncertain significance ★ ⚠ same type
- ACE2 p.Asn277Asp Uncertain significance ★ ⚠ same type
- ACE2 p.Asn682Ser Uncertain significance ★ ⚠ same type
- ACE2 p.Asn712Tyr 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/ace2-c-2309-plus-2t-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown