AFG3L2 p.Phe289=
c.867C>T · rs748162809 · VCV1806912
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0206%, nfe)
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 6.7 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 13.14 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0206%
European (non-Finnish) · 243/1,180,052 alleles
Filtering AF
0.0184%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0176%
Overall
0.0157%
253/1,614,106 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0206% | 4,856 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,498 |
| Admixed American | 0.00667% | 15,001 |
| East Asian | 0.00223% | 44,898 |
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.Phe289=
- Coding
- c.867C>T
- MANE Select
- NM_006796
- dbSNP
- rs748162809
- Type
- single nucleotide variant
- Location
- chr18:12358829 (GRCh38)
- Gene constraint
- LOEUF 0.724 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.07 · 2 PDB
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-phe289 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown