AFG3L2 p.Ala451=
c.1353C>T · rs374874087 · VCV729822
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.38 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5.3 | GERP -3.9 |
| Overall | ||
| CADD | 1.317 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,872 alleles
Filtering AF
0.0005%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000366%
Overall
0.000991%
16/1,614,038 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,872 |
| South Asian | 0.0022% | 45,532 |
| Admixed American | 0.00167% | 59,994 |
| African / African-American | 0.00133% | 74,998 |
| European (non-Finnish) | 0.000932% | 107,275 |
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.Ala451=
- Coding
- c.1353C>T
- MANE Select
- NM_006796
- dbSNP
- rs374874087
- Type
- single nucleotide variant
- Location
- chr18:12351379 (GRCh38)
- Gene constraint
- LOEUF 0.724 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.07 · 2 PDB
- Residue 451
- a β-strand
Similar variants
- AFG3L2 p.Arg41Ter Pathogenic/Likely pathogenic ★★ same type
- AFG3L2 p.Arg468Cys Pathogenic/Likely pathogenic ★★ same type
- AFG3L2 p.Arg68Ter Pathogenic ★★ same type
- AFG3L2 p.Gly337Glu Pathogenic ★★ same type
- AFG3L2 p.Gly385Ser Likely pathogenic ★★ same type
- AFG3L2 p.Gly671Arg Pathogenic ★★ same type
- AFG3L2 p.Met666Thr Pathogenic/Likely pathogenic ★★ same type
- AFG3L2 p.Met666Val Pathogenic/Likely pathogenic ★★ 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/afg3l2-p-ala451 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown