Is MEFV p.Arg278Pro (c.833G>C) pathogenic?

MEFV p.Arg278Pro (c.833G>C) is classified Uncertain significance in MEFV (ClinVar, Single submitter, 2 submitters; last evaluated 2018-02-06). AlphaMissense: likely benign (0.0874); Very rare (popmax 8.47e-05%, nfe); Associated with autoinflammatory syndrome.

What condition is associated with MEFV p.Arg278Pro (c.833G>C)?

MEFV p.Arg278Pro (c.833G>C) is associated with autoinflammatory syndrome, familial Mediterranean fever (ClinVar).

How common is MEFV p.Arg278Pro (c.833G>C) in the general population?

MEFV p.Arg278Pro (c.833G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about MEFV p.Arg278Pro (c.833G>C)?

AlphaMissense predicts likely benign (score 0.0874) — an in-silico prediction, not a clinical call.

MEFV p.Arg278Pro

c.833G>C · rs104895187 · VCV97547

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0874 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autoinflammatory syndrome

Computational evidence

Protein change
AlphaMissense	0.0874	likely benign
REVEL	0.246	benign-leaning
SaProt	LLR -7.06	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 -1.1	GERP -3.3
Regional constraint	o/e 1.16	unconstrained · MANE · 13 kb · p 2.1e-07 · regional, not allelic
Overall
CADD	1.982	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 8.47e-05% European (non-Finnish) · 1/1,180,046 alleles

Overall 6.19e-05% 1/1,614,258 alleles · very rare exomes 1/1,461,890 · genomes 0/152,368 · 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.Arg278Pro
Coding: c.833G>C
MANE Select: NM_000243
dbSNP: rs104895187
Type: single nucleotide variant
Location: chr16:3254235 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.64 · 11 PDB
Residue 278: the 'interaction with rela' region; the 'disordered' region

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

Disease context

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

Also linked: familial Mediterranean fever

Similar variants

MEFV p.Arg278Gln Uncertain significance ★★ ⚠ same residue
MEFV p.Arg278= Likely benign ★ 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-arg278pro (accessed [today's date]).

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