Is MEFV p.Pro183Arg (c.548C>G) pathogenic?

MEFV p.Pro183Arg (c.548C>G) is classified Uncertain significance in MEFV (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-03). AlphaMissense: likely benign (0.079); Ultra-rare (popmax 0.0369%, sas); Associated with familial Mediterranean fever.

What condition is associated with MEFV p.Pro183Arg (c.548C>G)?

MEFV p.Pro183Arg (c.548C>G) is associated with familial Mediterranean fever (ClinVar).

How common is MEFV p.Pro183Arg (c.548C>G) in the general population?

MEFV p.Pro183Arg (c.548C>G) is ultra-rare (popmax 0.0369%, sas) (gnomAD).

How is Familial Mediterranean fever inherited?

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

What do computational predictors say about MEFV p.Pro183Arg (c.548C>G)?

AlphaMissense predicts likely benign (score 0.079) — an in-silico prediction, not a clinical call.

MEFV p.Pro183Arg

c.548C>G · rs777009752 · VCV2190947

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.079 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0369%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial Mediterranean fever

Computational evidence

Protein change
AlphaMissense	0.079	likely benign
REVEL	0.164	moderately benign-leaning
SaProt	LLR -6.50	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.8	GERP -3.4
Regional constraint	o/e 1.16	unconstrained · MANE · 13 kb · p 2.1e-07 · regional, not allelic
Overall
CADD	0.087	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0369% South Asian · 32/86,668 alleles

Filtering AF 0.0268% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0234%

Overall 0.00225% 35/1,555,148 alleles · ultra-rare exomes 32/1,402,814 · genomes 3/152,334 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0369%	2,708
Remaining individualsnot grpmax-eligible	0.00166%	60,202
European (non-Finnish)	0.000173%	577,131

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.Pro183Arg
Coding: c.548C>G
MANE Select: NM_000243
dbSNP: rs777009752
Type: single nucleotide variant
Location: chr16:3254520 (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.Pro183= Conflicting classifications of pathogenicity ★ 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-pro183arg (accessed [today's date]).

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