Is MEFV p.Pro393= (c.1179C>T) pathogenic?

MEFV p.Pro393= (c.1179C>T) is classified Conflicting classifications of pathogenicity in MEFV (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-04). Ultra-rare (popmax 0.0466%, amr); Associated with sweet syndrome.

What condition is associated with MEFV p.Pro393= (c.1179C>T)?

MEFV p.Pro393= (c.1179C>T) is associated with sweet syndrome, familial Mediterranean fever, autosomal dominant, familial Mediterranean fever (ClinVar).

How common is MEFV p.Pro393= (c.1179C>T) in the general population?

MEFV p.Pro393= (c.1179C>T) is ultra-rare (popmax 0.0466%, amr) (gnomAD).

How is Sweet syndrome inherited?

Typically Multigenic/multifactorial (Orphanet). A genetic counselor can assess individual risk for a family.

MEFV p.Pro393=

c.1179C>T · rs104895082 · VCV97434

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0466%, amr)

Conditions

sweet 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 0.077	GERP -4.4, phastCons 0.47
Overall
CADD	6.958	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0466% Admixed American · 28/60,022 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0286%

Overall 0.0026% 42/1,614,196 alleles · ultra-rare exomes 35/1,461,848 · genomes 7/152,348 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0466%	2,144
South Asian	0.00549%	18,216
East Asian	0.00223%	44,888
Remaining individualsnot grpmax-eligible	0.0016%	62,512
European (non-Finnish)	0.000593%	168,576

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.Pro393=
Coding: c.1179C>T
MANE Select: NM_000243
dbSNP: rs104895082
Type: single nucleotide variant
Location: chr16:3249512 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.64 · 11 PDB

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

Disease context

sweet syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial Mediterranean fever, autosomal dominant familial Mediterranean fever

For Sweet syndrome (Orphanet):

Inheritance: Multigenic/multifactorial
Onset: Adult

Similar variants

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
MEFV p.Ala768Gly 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-pro393 (accessed [today's date]).

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