AFG3L2 c.1663+1G>A
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 +1 | canonical splice dinucleotide (donor +1) · inside the BP7-excluded zone |
| SpliceAI | Δ0.99 | donor loss · deltas |
| Pangolin | Δ0.87 | loss · gain 0.02 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 33.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
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
- AFG3L2
- Coding
- c.1663+1G>A
- MANE Select
- NM_006796
- Type
- single nucleotide variant
- Location
- chr18:12348272 (GRCh38)
- Gene constraint
- LOEUF 0.724 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.07 · 2 PDB
Similar variants
- AFG3L2 p.Arg468Cys Pathogenic/Likely pathogenic ★★ same condition
- AFG3L2 p.Arg68Ter Pathogenic ★★ same condition
- AFG3L2 p.Gly337Glu Pathogenic ★★ same condition
- AFG3L2 p.Gly385Ser Likely pathogenic ★★ same condition
- AFG3L2 p.Gly671Arg Pathogenic ★★ same condition
- AFG3L2 p.Met666Thr Pathogenic/Likely pathogenic ★★ same condition
- AFG3L2 p.Met666Val Pathogenic/Likely pathogenic ★★ same condition
- AFG3L2 p.Thr654Ile Likely 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/afg3l2-c-1663-plus-1g-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown