MEFV p.Ala457=
c.1371G>A · rs761470030 · VCV1567260
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Conditions
2
Inborn genetic diseases
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 0.27 | GERP -3, phastCons 0.004 |
| Overall | ||
| CADD | 4.686 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,062 alleles
Filtering AF
0.000739%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000366%
Overall
0.000929%
15/1,614,138 alleles · ultra-rare
exomes 15/1,461,844 · genomes 0/152,294 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,062 |
| East Asian | 0.00446% | 22,443 |
| South Asian | 0.0011% | 91,080 |
| European (non-Finnish) | 0.000932% | 107,276 |
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
- MEFV
- Protein
- p.Ala457=
- Coding
- c.1371G>A
- MANE Select
- NM_000243
- dbSNP
- rs761470030
- Type
- single nucleotide variant
- Location
- chr16:3247232 (GRCh38)
- Gene constraint
- LOEUF 1.147 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.64 · 11 PDB
- Residue 457
- an α-helix; the 'required for homotrimerization and induction of pyroptosomes' region
Similar variants
- MEFV p.Ala457Val Conflicting classifications of pathogenicity ★ ⚠ same residue
- MEFV p.Arg761His Pathogenic/Likely pathogenic ★★ ⚠ same condition
- MEFV p.Ser242Arg Pathogenic/Likely pathogenic ★★ same condition
- MEFV p.Val726Ala Pathogenic/Likely pathogenic ★★ ⚠ same condition
- MEFV c.*845C>T Uncertain significance ★★ same condition
- MEFV p.Ala193Thr Uncertain significance ★★ ⚠ same condition
- MEFV p.Ala2Gly Uncertain significance ★★ ⚠ same condition
- MEFV p.Ala416Thr Uncertain significance ★★ ⚠ 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/mefv-p-ala457 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown