# NM_000243.2:c.(?_911)_(1356_?)del

https://sugi.bio/variant/mefv-c-911

## Summary

**MEFV c.(?_911** is classified **Likely pathogenic** in MEFV (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-04). Associated with familial Mediterranean fever, autosomal dominant.

**At a glance:** Likely pathogenic · review: Single submitter · 1 submitter · 1 linked condition

## For patients & families {#patients}

This is a change in the MEFV gene that is considered likely disease-causing, submitted by 1 submitter, and is linked to familial Mediterranean fever, autosomal dominant.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

|  |  |
| --- | --- |
| Typical inheritance (of this condition) | Autosomal dominant, Autosomal recessive |
| Age of onset (of this condition) | Adolescent, Adult, Childhood, Infancy |
| Prevalence | >1 / 1000 (Turkey) |
| Diagnostic panels | MEFV is a diagnostic-grade gene on 6 Genomics England panels |

**Commonly reported features of Familial Mediterranean fever** (across patients with this condition; presentation varies — frequencies from Orphanet):

- Constipation — Very frequent (99-80%)
- Abdominal pain — Very frequent (99-80%)
- Arthralgia — Very frequent (99-80%)
- Myalgia — Very frequent (99-80%)
- Fever — Very frequent (99-80%)
- Nausea and vomiting — Very frequent (99-80%)
- Proteinuria — Frequent (79-30%)
- Irritability — Frequent (79-30%)

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0015069/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [MEFV](https://sugi.bio/atlas/gene/MEFV/) |
| Coding change (HGVS c.) | c.(?_911 |
| MANE Select transcript | [NM_000243](https://www.ncbi.nlm.nih.gov/nuccore/NM_000243) |
| Variant type | Deletion |
| ClinVar | [VCV987917](https://www.ncbi.nlm.nih.gov/clinvar/variation/987917/) |

**All HGVS expressions:** `LRG_190t1:c.(?_911)_(1356_?)del`

## Gene constraint & dosage {#gene-context}

**MEFV** population constraint: LOEUF 1.147, pLI 2.305e-19, missense-Z -1.6136; ClinGen dosage — haploinsufficiency 0/3, triplosensitivity 0/3. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

Curated gene–disease validity (ClinGen):

- **familial Mediterranean fever** — Definitive (SD)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 73.64, 50% of residues very-high.

**11 experimental structure(s)** (PDB): [2MPC](https://www.rcsb.org/structure/2MPC), [2WL1](https://www.rcsb.org/structure/2WL1), [4CG4](https://www.rcsb.org/structure/4CG4), [8C28](https://www.rcsb.org/structure/8C28), [8C2Y](https://www.rcsb.org/structure/8C2Y), [8C30](https://www.rcsb.org/structure/8C30).

## What this gene does {#gene-function}

*Describes the biological roles of MEFV (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** MEFV's established molecular role includes actin binding. In Reactome, MEFV is annotated in disease pathway(s) including **Purinergic signaling in leishmaniasis infection**.

**Disease mechanism (Reactome):** MEFV loss or alteration is curated in [Purinergic signaling in leishmaniasis infection](https://reactome.org/content/detail/R-HSA-9660826).

### Pathways affected {#pathways}

MEFV participates in **2 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| ⚕ [Purinergic signaling in leishmaniasis infection](https://reactome.org/content/detail/R-HSA-9660826) | curated |
| [The NLRP3 inflammasome](https://reactome.org/content/detail/R-HSA-844456) | curated |

### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** actin binding, identical protein binding.

**Biological process:** inflammatory response, positive regulation of autophagy, regulation of interleukin-1 beta production, negative regulation of interleukin-1 beta production, negative regulation of interleukin-12 production, positive regulation of interleukin-1 beta production.

## Clinical significance {#significance}

**Likely pathogenic** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2020-10-04.

**Submitter consensus:** unanimous (1/1 Likely pathogenic).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Dubai Health Genomic Medicine Center, Dubai Health | Likely pathogenic | criteria provided, single submitter | clinical testing | 2020-10-04 |

## Associated conditions {#conditions}

[familial Mediterranean fever, autosomal dominant](https://sugi.bio/atlas/disease/familial-mediterranean-fever-autosomal-dominant/).

**Reported phenotype names (ClinVar):** Familial Mediterranean fever, autosomal dominant, Dominant Familial Mediterranean Fever, FMF, AUTOSOMAL DOMINANT.

## Similar variants {#similar}

Related MEFV variant pages (same residue, condition, or type): [MEFV p.Gly137fs](/variant/mefv-p-gly137fs), [MEFV p.Leu182fs](/variant/mefv-p-leu182fs), [MEFV p.Thr771fs](/variant/mefv-p-thr771fs), [MEFV p.Arg761His](/variant/mefv-p-arg761his), [MEFV p.Ser242Arg](/variant/mefv-p-ser242arg), [MEFV p.Val726Ala](/variant/mefv-p-val726ala), [MEFV p.Ala2Gly](/variant/mefv-p-ala2gly), [MEFV p.Ala416Thr](/variant/mefv-p-ala416thr).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-15); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-10-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 987917). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*