AFG3L2 p.Arg551Ter
c.1651C>T · rs149121681 · VCV3251301
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 13 of 17 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Pangolin | Δ0.21 | loss · gain 0.01 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 4.4 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 47.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,444 |
| African / African-Americangrpmax | 0.00134% | 74,844 |
| European (non-Finnish) | 0.000933% | 107,178 |
Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- Protein
- p.Arg551Ter
- Coding
- c.1651C>T
- MANE Select
- NM_006796
- dbSNP
- rs149121681
- Type
- single nucleotide variant
- Location
- chr18:12348285 (GRCh38)
- Gene constraint
- LOEUF 0.724 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.07 · 2 PDB
- Residue 551
- an α-helix
Disease context
spinocerebellar ataxia type 28 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Spinocerebellar ataxia type 28 (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- Childhood
Similar variants
- 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
- AFG3L2 p.Tyr689His Pathogenic/Likely pathogenic ★★ same condition
- AFG3L2 p.Arg599His Uncertain significance ★★ ⚠ same condition
- AFG3L2 p.Arg783Trp Uncertain significance ★★ ⚠ 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-p-arg551ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown