AFG3L2 p.Glu567=
c.1701G>A · VCV3771382
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, mid)
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 1.3 | GERP 0.87, phastCons 1 |
| Overall | ||
| CADD | 7.979 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,052 alleles
Filtering AF
0.00583%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00242%
Overall
0.0013%
21/1,614,198 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,026 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0101% | 9,869 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,252 |
| African / African-American | 0.00133% | 75,058 |
| European (non-Finnish) | 0.0011% | 90,772 |
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.Glu567=
- Coding
- c.1701G>A
- MANE Select
- NM_006796
- Type
- single nucleotide variant
- Location
- chr18:12344210 (GRCh38)
- Gene constraint
- LOEUF 0.724 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.07 · 2 PDB
- Residue 567
- 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-glu567 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown