MFN2 p.Arg274=
c.822G>A · rs528330690 · VCV1640286
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0173%, afr)
Conditions
1
Charcot-Marie-Tooth disease type 2
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 3 | GERP 0.92, phastCons 1 |
| Overall | ||
| CADD | 11.63 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0173%
African / African-American · 13/75,044 alleles
Filtering AF
0.0102%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00811%
Overall
0.00155%
25/1,613,582 alleles · ultra-rare
exomes 19/1,461,254 · genomes 6/152,328 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0173% | 5,773 |
| Remaining individualsnot grpmax-eligible | 0.00961% | 10,408 |
| European (non-Finnish) | 0.000509% | 196,651 |
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
- MFN2
- Protein
- p.Arg274=
- Coding
- c.822G>A
- MANE Select
- NM_014874
- dbSNP
- rs528330690
- Type
- single nucleotide variant
- Location
- chr1:12001406 (GRCh38)
- Gene constraint
- LOEUF 0.602 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 81.94 · 3 PDB
- Residue 274
- an α-helix; the dynamin-type g domain
Similar variants
- MFN2 p.Arg274Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
- MFN2 p.Arg274Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
- MFN2 p.Arg274_Arg275del Pathogenic ★ same residue
- MFN2 c.1160+1G>A Likely pathogenic ★★ same condition
- MFN2 c.475-1G>C Pathogenic ★★ same condition
- MFN2 p.Ala166Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
- MFN2 p.Ala220Thr Pathogenic/Likely pathogenic ★★ same condition
- MFN2 p.Ala383Val Pathogenic/Likely pathogenic ★★ ⚠ 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/mfn2-p-arg274 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown