Is MEFV p.Pro183= (c.549G>A) pathogenic?

MEFV p.Pro183= (c.549G>A) is classified Conflicting classifications of pathogenicity in MEFV (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-26). Ultra-rare (popmax 0.0132%, nfe); Associated with familial Mediterranean fever.

What condition is associated with MEFV p.Pro183= (c.549G>A)?

MEFV p.Pro183= (c.549G>A) is associated with familial Mediterranean fever (ClinVar).

How common is MEFV p.Pro183= (c.549G>A) in the general population?

MEFV p.Pro183= (c.549G>A) is ultra-rare (popmax 0.0132%, nfe) (gnomAD).

How is Familial Mediterranean fever inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MEFV p.Pro183=

c.549G>A · rs587781035 · VCV138207

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, nfe)

Conditions

familial Mediterranean fever

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 -2.2	GERP -3.4
Overall
CADD	0.424	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0132% European (non-Finnish) · 153/1,154,734 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.0115% 179/1,556,050 alleles · ultra-rare exomes 163/1,403,840 · genomes 16/152,210 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0282%	3,541
European (non-Finnish)grpmax	0.0132%	7,547
African / African-American	0.0109%	9,181
East Asian	0.00236%	42,358

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro183=
Coding: c.549G>A
MANE Select: NM_000243
dbSNP: rs587781035
Type: single nucleotide variant
Location: chr16:3254519 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.64 · 11 PDB
Residue 183: the 'disordered' region

Full MEFV gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial Mediterranean fever — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial Mediterranean fever (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: >1 / 1000 (Turkey)

Similar variants

MEFV p.Pro183Arg Uncertain significance ★ ⚠ same residue
MEFV p.Pro183Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
MEFV p.Pro183Ser Uncertain significance ★ ⚠ same residue
MEFV p.Pro183Thr 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

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-pro183 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown