MEFV p.Val33=
c.99G>A · rs767848974 · VCV1101415
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00915%, nfe)
Conditions
2
autoinflammatory syndrome
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 -2.5, phastCons 1 |
| Overall | ||
| CADD | 8.497 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00915%
European (non-Finnish) · 108/1,180,058 alleles
Filtering AF
0.00774%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00719%
Overall
0.00669%
108/1,614,098 alleles · very rare
exomes 104/1,461,894 · genomes 4/152,204 · joint denominator
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.Val33=
- Coding
- c.99G>A
- MANE Select
- NM_000243
- dbSNP
- rs767848974
- Type
- single nucleotide variant
- Location
- chr16:3256489 (GRCh38)
- Gene constraint
- LOEUF 1.147 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.64 · 11 PDB
- Residue 33
- the pyrin domain; a UniProt-annotated variant site (in); an α-helix
Similar variants
- MEFV p.Val33Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- MEFV p.Val33Gly Uncertain significance ★ ⚠ 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
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-val33 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown