AFG3L2 p.Val653=
c.1959A>G · rs371146948 · VCV2033720
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00133%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.028 | GERP -3.4, phastCons 0.83 |
| Overall | ||
| CADD | 3.809 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00133%
African / African-American · 1/74,952 alleles
Overall
0.000657%
1/152,240 alleles · very rare
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.Val653=
- Coding
- c.1959A>G
- MANE Select
- NM_006796
- dbSNP
- rs371146948
- Type
- single nucleotide variant
- Location
- chr18:12340222 (GRCh38)
- Gene constraint
- LOEUF 0.724 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.07 · 2 PDB
- Residue 653
- an α-helix
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-val653 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown